A Review of Factors Influencing Anxiety and Depression in Persons with Multiple Sclerosis during the COVID-19 Pandemic Multiple sclerosis, COVID-19, low-dose naltrexone, anxiety
Main Article Content
Patricia J. McLaughlin
Laura B. Odom
Ian S. Zagon
http://orcid.org/0000-0002-4221-6745
http://orcid.org/0000-0002-4221-6745
Abstract
Patients with multiple sclerosis have been subjected to extra levels of stress during the COVID-19 pandemic when they were singled out by governmental regulatory agencies as sufficiently immune-compromised persons that should be in the first group to receive the untested, new COVID-19 vaccine. The designation of these persons in such a high-risk group compounded their anxiety and depression. Early in the disease in 2020-2021, little was known about the disease, the vaccine, or whether their disease-modifying therapies for multiple sclerosis were subjecting them to more immunomodulatory suppression. This review is not comprehensive of all articles written on COVID-19 and multiple sclerosis, but selectively looks at research on COVID-19 and use of low-doses of naltrexone as treatment. Specific causes for anxiety and depression are discussed in light of evidence that suggests that the length of disease, rather than age, sex, or therapy leads to more anxiety. Low-dose naltrexone in combination with other disease-modifying therapies, or alone, reduced the perceived levels of anxiety. These data suggest that clinicians may want to prescribe low-dose naltrexone for early-stage multiple sclerosis patients.
Article Details
How to Cite
MCLAUGHLIN, Patricia J.; ODOM, Laura B.; ZAGON, Ian S..
A Review of Factors Influencing Anxiety and Depression in Persons with Multiple Sclerosis during the COVID-19 Pandemic.
Medical Research Archives, [S.l.], v. 11, n. 6, june 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3964>. Date accessed: 15 may 2024.
doi: https://doi.org/10.18103/mra.v11i6.3964.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. National Multiple Sclerosis Society. Multiple sclerosis and COVID-19. Accessed April 2023.
https://www.nationalmssociety.org/coronavirus-covid-19-information
2. Centers for Disease Control and Prevention. CDC simplifies COVID-19 vaccine recommendations. Accessed April 2023.
https://www.cdc.gov/media/releases/2023/s0419-covid-vaccines.html
3. Capone F, Rossi M, Cruciani A, Motolese F, Pilato F, Di Lazzaro V. Safety, immunogenicity, efficacy, and acceptability of COVID-19 vaccination in people with multiple sclerosis: a narrative review. Neural Regen Res. 2023;18:284-288. https://doi.org/10.4103/1673-5374.346539
4. Zheng C, Kar I, Chen CK, Sau C, Woodson S, Serra A, Abboud H. Multiple sclerosis disease-modifying therapy and the COVID-19 pandemic: Implications on the risk of infection and future vaccination. CNS Drugs. 2020;34:879-896. doi: 10.1007/s40263-020-00756-y.
5. Sormani MP, Schiavetti I, Carmisciano L, Cordioli C, Filippi M, Radaelli M, Immovilli P, Capobianco M, De Rossi N, Brichetto G, Cocco E, Scandellari C, Cavalla P, Pesci I, Zito A, Confalonieri P, Marfia GA, Perini P, Inglese M, Trojano M, Brescia Morra V, Tedeschi G, Comi G, Battaglia MA, Patti F, Salvetti M and MuSC-19 Study Group. COVID-19 severity in multiple sclerosis. Putting data into context. Neurol Neuroimmunol Neuroinflamm. 2021;9:e1105.
doi: 10.1212/NXI.0000000000001105.
6. Etemadifar M, Nouri H, Pitzalis M, Idda ML, Salari M, Baratian M, Mahdavi S, Abhari AP, Sedaghat N. Multiple Sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis. J. Neurol Neurosurg Psychiat. 2022;93:986-994.
7. Cross AH, Delgado S, Habek M, Davydovshkaya M, Ward BJ, Cree BAC, Totlyan N, Pingili R, Mancione L, Hu X, Sullivan R, Su W, Zielman R, Das Gupta A, Montalban X, Winthrop K. COVID-19 outcomes and vaccination in people with relapse-remitting multiple sclerosis treated with Ofatumumab. Neurol Ther. 2022;11:741-758.
8. Reder AT, Centronze D, Naylor ML, Nagpal A, Rajbhandari J, Altincatal A, Kim M, Berdofe A, Radhakrishnan M, Jung E, Sandrock AW, Smirnakis K, Popescu C, de Moor C. COVID-19 in patients with multiple sclerosis: Associations with disease-modifying therapies. CNS Drugs. 2021; 35:317-330.
9. Alirezael M, Eskandarieh S, Sahraian MA, Moghadasi AN. Depression, anxiety, and fear of COVID-19 in patients with multiple sclerosis in pandemic era: a cross-sectional study. Neurol Sci. 2022;43:59-66
10. Ramezani N, Ashtari F, Bastami EA< Ghaderi K, Hosseini SM, Naeini MK, Rajabi F, Adibi I. Fear and anxiety in patients with multiple sclerosis during COVID-19 pandemic: report of an Iranian population. Mult Scler Relat Disord. 2021;50:102798
11. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res. 2002;52:69 77 doi: 10.1016/s0022-3999(01)00296-3
12. McLaughlin PJ, Odom, LB, Arnett PA, Thomas GA, Orehek S, Zagon IS. Length of disease more than therapy impacts anxiety and depression in persons with multiple sclerosis. Neurol Neurosci. 2023;4.
13. Strober LB, Arnett PA. Depression in multiple sclerosis: The utility of common self-report instruments and development of a disease-specific measure. J Clin Exp Neuropsych 2015;37:722-732.
14. McLaughlin PJ, Odom LB, Arnett PA, Orehek S, Thomas GA, Zagon IS. Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic. Int Immunopharmacol 2022;113(Pt B):109438. doi: 10.1016/j.intimp.2022.109438
15. McLaughlin PJ and Zagon IS. Duration of opioid receptor blockade determines clinical response. Biochem Pharmacol. 2015; 97:236-246.
16. Ludwig MD, Zagon IS, McLaughlin PJ. Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone. Exp Biol Med 2017;242(15):1524-1533. doi: 10.1177/1535370217724791
17. Ludwig MD, Turel AP, Zagon IS, McLaughlin PJ. Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis. Mult Scler J Exp Trans Clin. 2016;
2:2055217316672242.
doi: 10.1177/2055217316672242.
18. Patel C, Thomas G, Zomorodi N, Zagon IS, McLaughlin PJ . β-endorphin and opioid growth factor as biomarkers of physical ability in Multiple Sclerosis. Mult Scler Relat Disord 2021;50:102808.
doi: 10.1016/j.msard.2021.102868
19. Ludwig MD, Zagon IS, McLaughlin PJ. Modulation of the OGF-OGFr pathway alters cytokine profiles in experimental autoimmune encephalomyelitis and multiple sclerosis. Exp Biol Med. 2018;
243:361-369.
20. Patel C, Zagon IS, Pearce-Clawson M, McLaughlin PJ. Timing of treatment with an endogenous opioid alters immune response and spinal cord pathology in female mice with experimental autoimmune encephalomyelitis. J Neurosci Res. 2021;100:551-563. Doi:10.1002/jnr.24983
21. Paulides E, Lie MRKL, van der Woude CJ. Low-dose naltrexone for the induction of remission in patients with mild to moderate Crohn’s disease: protocol for the randomized, double-blinded, placebo-controlled, multicentre LDN Crohn Study. BMJ Open 2022;12:e058358.
22. Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: a randomized placebo-controlled trial. Dig Dis Sci. 2011;56:2088-97.
23. Tawfik DI, Osman AS, Tolba NH, Khattab A, Ab del-Salam LO, Kamel MM. Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn’s disease in rats. Neuropeptides 2016;59:39-45. doi: 10.1016/j-npep.2016.06.003.
24. Siembida J, Johnson B. Depression in fibromyalgia patients may require low-dose naltrexone to respond: A case report. Cureus 2022;14(2):e22677.
25. Parkitny L, Younger L. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for fibromyalgia. Biomedicines 2017;5:16.
26. Patten DK, Schultz BG, Berlau DJ. The safety and efficacy of low-dose naltrexone in the management of chronic pain and inflammation in multiple sclerosis, fibromyalgia, Crohn’s disease, and other chronic pain disorders. Pharmacotherapy 2018;38:382-389.
doi: 10.1002/phar.2086
27. Yang J, Shin K-M, DoA, Bierle DM, Dabrh AMA, In Z, Bauer BA, Mohabbat AB. The safety and efficacy of low-dose naltrexone in patients with fibromyalgia: A systematic review. J Pain Res. 2023;16:1017-1023.
28. Soin A, Soin Y, Dann T, Buenavenntura R, Ferguson K, Atluri S, Sachdeva H, Sudarshan G, Akbik H, Italiano J. Low-dose naltrexone use for patients with chronic regional pain syndrome: A systematic literature review. Pain Physician 2021; 24(4):E393-E406.
29. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as anovel anti-inflammatorytreatment for chronic pain. Clin Rheumatol 2014; 33: 451-459
doi: 10.1007/s10067-014-2517-2.
30. Dieckmann G, Ozmen MC, Cox SM, Engert RC, Hamrah P. Low-dose naltrexone is effective and well-tolerated formodulating symptoms in patients with neuropthatic corneal pain. Ocul Surf 2021; 20:33-38.
31. Pitt B, Tate AM, Gluck D, Rosenson RS, Goonewardena SN. Repurposing low-dose naltrexone for the prevention and treatment of immunothrombosis in COVID-19. Eur Heart J Cardiovasc Pharmacother. 2022;8:402-405. Doi: 10.1093/ehjcvp/pvac014
32. Choubey A, Dehury B, Kuman S, Medhi B, Mondal P. Naltrexone a potential therapeutic candidate for COVID-19. J. BioMol Struct Dyn 2020:1-8. doi:10.1080/07391102.2020.1820379.
33. O’Kelly B, Vidal L, McHugh T, Woo J, Avramovic G, Lambert JS. Safety and efficacy of low dose naltrexone in a long covid cohort: an interventional pre-post study. Brain Behavior Immunity – Health 2022;24:100485
34. Mischoulon D, Hylek L, Yeung AS, Clain AJ, Baer L, Cusin C, Ionescu DF, Alpert JE, Soskin DP, Fava M. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. J Affect Dis. 2017;208:6-14.
https://www.nationalmssociety.org/coronavirus-covid-19-information
2. Centers for Disease Control and Prevention. CDC simplifies COVID-19 vaccine recommendations. Accessed April 2023.
https://www.cdc.gov/media/releases/2023/s0419-covid-vaccines.html
3. Capone F, Rossi M, Cruciani A, Motolese F, Pilato F, Di Lazzaro V. Safety, immunogenicity, efficacy, and acceptability of COVID-19 vaccination in people with multiple sclerosis: a narrative review. Neural Regen Res. 2023;18:284-288. https://doi.org/10.4103/1673-5374.346539
4. Zheng C, Kar I, Chen CK, Sau C, Woodson S, Serra A, Abboud H. Multiple sclerosis disease-modifying therapy and the COVID-19 pandemic: Implications on the risk of infection and future vaccination. CNS Drugs. 2020;34:879-896. doi: 10.1007/s40263-020-00756-y.
5. Sormani MP, Schiavetti I, Carmisciano L, Cordioli C, Filippi M, Radaelli M, Immovilli P, Capobianco M, De Rossi N, Brichetto G, Cocco E, Scandellari C, Cavalla P, Pesci I, Zito A, Confalonieri P, Marfia GA, Perini P, Inglese M, Trojano M, Brescia Morra V, Tedeschi G, Comi G, Battaglia MA, Patti F, Salvetti M and MuSC-19 Study Group. COVID-19 severity in multiple sclerosis. Putting data into context. Neurol Neuroimmunol Neuroinflamm. 2021;9:e1105.
doi: 10.1212/NXI.0000000000001105.
6. Etemadifar M, Nouri H, Pitzalis M, Idda ML, Salari M, Baratian M, Mahdavi S, Abhari AP, Sedaghat N. Multiple Sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis. J. Neurol Neurosurg Psychiat. 2022;93:986-994.
7. Cross AH, Delgado S, Habek M, Davydovshkaya M, Ward BJ, Cree BAC, Totlyan N, Pingili R, Mancione L, Hu X, Sullivan R, Su W, Zielman R, Das Gupta A, Montalban X, Winthrop K. COVID-19 outcomes and vaccination in people with relapse-remitting multiple sclerosis treated with Ofatumumab. Neurol Ther. 2022;11:741-758.
8. Reder AT, Centronze D, Naylor ML, Nagpal A, Rajbhandari J, Altincatal A, Kim M, Berdofe A, Radhakrishnan M, Jung E, Sandrock AW, Smirnakis K, Popescu C, de Moor C. COVID-19 in patients with multiple sclerosis: Associations with disease-modifying therapies. CNS Drugs. 2021; 35:317-330.
9. Alirezael M, Eskandarieh S, Sahraian MA, Moghadasi AN. Depression, anxiety, and fear of COVID-19 in patients with multiple sclerosis in pandemic era: a cross-sectional study. Neurol Sci. 2022;43:59-66
10. Ramezani N, Ashtari F, Bastami EA< Ghaderi K, Hosseini SM, Naeini MK, Rajabi F, Adibi I. Fear and anxiety in patients with multiple sclerosis during COVID-19 pandemic: report of an Iranian population. Mult Scler Relat Disord. 2021;50:102798
11. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res. 2002;52:69 77 doi: 10.1016/s0022-3999(01)00296-3
12. McLaughlin PJ, Odom, LB, Arnett PA, Thomas GA, Orehek S, Zagon IS. Length of disease more than therapy impacts anxiety and depression in persons with multiple sclerosis. Neurol Neurosci. 2023;4.
13. Strober LB, Arnett PA. Depression in multiple sclerosis: The utility of common self-report instruments and development of a disease-specific measure. J Clin Exp Neuropsych 2015;37:722-732.
14. McLaughlin PJ, Odom LB, Arnett PA, Orehek S, Thomas GA, Zagon IS. Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic. Int Immunopharmacol 2022;113(Pt B):109438. doi: 10.1016/j.intimp.2022.109438
15. McLaughlin PJ and Zagon IS. Duration of opioid receptor blockade determines clinical response. Biochem Pharmacol. 2015; 97:236-246.
16. Ludwig MD, Zagon IS, McLaughlin PJ. Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone. Exp Biol Med 2017;242(15):1524-1533. doi: 10.1177/1535370217724791
17. Ludwig MD, Turel AP, Zagon IS, McLaughlin PJ. Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis. Mult Scler J Exp Trans Clin. 2016;
2:2055217316672242.
doi: 10.1177/2055217316672242.
18. Patel C, Thomas G, Zomorodi N, Zagon IS, McLaughlin PJ . β-endorphin and opioid growth factor as biomarkers of physical ability in Multiple Sclerosis. Mult Scler Relat Disord 2021;50:102808.
doi: 10.1016/j.msard.2021.102868
19. Ludwig MD, Zagon IS, McLaughlin PJ. Modulation of the OGF-OGFr pathway alters cytokine profiles in experimental autoimmune encephalomyelitis and multiple sclerosis. Exp Biol Med. 2018;
243:361-369.
20. Patel C, Zagon IS, Pearce-Clawson M, McLaughlin PJ. Timing of treatment with an endogenous opioid alters immune response and spinal cord pathology in female mice with experimental autoimmune encephalomyelitis. J Neurosci Res. 2021;100:551-563. Doi:10.1002/jnr.24983
21. Paulides E, Lie MRKL, van der Woude CJ. Low-dose naltrexone for the induction of remission in patients with mild to moderate Crohn’s disease: protocol for the randomized, double-blinded, placebo-controlled, multicentre LDN Crohn Study. BMJ Open 2022;12:e058358.
22. Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: a randomized placebo-controlled trial. Dig Dis Sci. 2011;56:2088-97.
23. Tawfik DI, Osman AS, Tolba NH, Khattab A, Ab del-Salam LO, Kamel MM. Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn’s disease in rats. Neuropeptides 2016;59:39-45. doi: 10.1016/j-npep.2016.06.003.
24. Siembida J, Johnson B. Depression in fibromyalgia patients may require low-dose naltrexone to respond: A case report. Cureus 2022;14(2):e22677.
25. Parkitny L, Younger L. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for fibromyalgia. Biomedicines 2017;5:16.
26. Patten DK, Schultz BG, Berlau DJ. The safety and efficacy of low-dose naltrexone in the management of chronic pain and inflammation in multiple sclerosis, fibromyalgia, Crohn’s disease, and other chronic pain disorders. Pharmacotherapy 2018;38:382-389.
doi: 10.1002/phar.2086
27. Yang J, Shin K-M, DoA, Bierle DM, Dabrh AMA, In Z, Bauer BA, Mohabbat AB. The safety and efficacy of low-dose naltrexone in patients with fibromyalgia: A systematic review. J Pain Res. 2023;16:1017-1023.
28. Soin A, Soin Y, Dann T, Buenavenntura R, Ferguson K, Atluri S, Sachdeva H, Sudarshan G, Akbik H, Italiano J. Low-dose naltrexone use for patients with chronic regional pain syndrome: A systematic literature review. Pain Physician 2021; 24(4):E393-E406.
29. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as anovel anti-inflammatorytreatment for chronic pain. Clin Rheumatol 2014; 33: 451-459
doi: 10.1007/s10067-014-2517-2.
30. Dieckmann G, Ozmen MC, Cox SM, Engert RC, Hamrah P. Low-dose naltrexone is effective and well-tolerated formodulating symptoms in patients with neuropthatic corneal pain. Ocul Surf 2021; 20:33-38.
31. Pitt B, Tate AM, Gluck D, Rosenson RS, Goonewardena SN. Repurposing low-dose naltrexone for the prevention and treatment of immunothrombosis in COVID-19. Eur Heart J Cardiovasc Pharmacother. 2022;8:402-405. Doi: 10.1093/ehjcvp/pvac014
32. Choubey A, Dehury B, Kuman S, Medhi B, Mondal P. Naltrexone a potential therapeutic candidate for COVID-19. J. BioMol Struct Dyn 2020:1-8. doi:10.1080/07391102.2020.1820379.
33. O’Kelly B, Vidal L, McHugh T, Woo J, Avramovic G, Lambert JS. Safety and efficacy of low dose naltrexone in a long covid cohort: an interventional pre-post study. Brain Behavior Immunity – Health 2022;24:100485
34. Mischoulon D, Hylek L, Yeung AS, Clain AJ, Baer L, Cusin C, Ionescu DF, Alpert JE, Soskin DP, Fava M. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. J Affect Dis. 2017;208:6-14.