Treatment of sleep disturbances associated with chronic non-specific low back pain: results of prospective randomized multicenter open-label clinical trial

Close metadata

OBJECTIVE

A comparative study of the effectiveness and safety of novel combination naproxen sodium and diphenhydramine in subjects with low back pain along with transient insomnia.

MATERIAL AND METHODS

It was an open label, randomized, comparative, parallel group and multi-center clinical study. Subjects were randomised into one of three treatment arms: naproxen sodium 440 mg/diphenhydramine 50 mg, naproxen sodium 550 mg, Paracetamol 1000 mg/diphenhydramine 50 mg. All the subjects were advised to apply study drug ones before sleep for 3 days. All subjects also received naproxen sodium 275 mg as background therapy. The primary end-point was wake time after sleep onset (WASO) measured by actigraphy. Other secondary sleep and pain end-points were also assessed.

RESULTS

Efficacy analysis was performed for intent-to-treat population (n=235 subjects). naproxen sodium 440 mg/diphenhydramine 50 mg combination showed significant improvements in WASO vs. naproxen sodium 550 mg (–42 min p=0.0174), while differences vs. Paracetamol 1000 mg/diphenhydramine 50 mg (–30 min, p=0.0891) were not significant. According to the average pain intensity difference in the lumbosacral spine combination product naproxen sodium 440 mg/diphenhydramine 50 mg was significantly improved compared with naproxen sodium 550 mg (–9.42, p<0.001) and Paracetamol 1000 mg/diphenhydramine 50 (–7.15, p<0.05).

CONCLUSION

Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.

Keywords:

neurology

low back pain

insomnia

treatment

insomnia

naproxen

diphenhydramine

Authors:

Barantsevich E.R.

Pavlov First Saint Petersburg State Medical University

ORCID: 0000-0003-3804-3877

Karakulova Yu.V.

Wagner Perm State Medical University

SPIN RSCI: 5066-6556
Scopus AuthorID: 12647536000
ResearcherID: D-2553-2018
ORCID: 0000-0002-7536-2060

Baranova N.S.

Yaroslavl State Medical University

Morzhukhina M.V.

Yaroslavl Hospital No. 2

Received:

22.11.2022

Accepted:

01.12.2022

List of references:

Bhaskar S, Hemavathy D, Prasad S. Prevalence of chronic insomnia in adult patients and its correlation with medical comorbidities. J Family Med Prim Care. 2016;5(4):780-784. https://doi.org/10.4103/2249-4863.201153
Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005. American Academy of Sleep Medicine. International Classification of Sleep Disorders.
Roth T. Insomnia: definition, prevalence, etiology, and consequences. J Clin Sleep Med. 2007;3(5 suppl):7-10.
Yakupov EYa. Sleep disorders as an interdisciplinary problem. Medical advice. 2016;11:42-47. (In Russ.).
Poluektov MG, Pchelina PV. Is secondary insomnia secondary? Non-specific treatment options with melatonin preparations. Medical Council. 2014;18:51-57.(In Russ.).
Vinogradov DK, Doronina OB. Characteristics of Sleep disorders in Patients with Chronic Back pain. J Clin Pract. 2019;10(2):46-52. (In Russ.). https://doi.org/10.17816/clinpract10246-52
Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. Sleep. 1999;22(suppl 2):347-353.
Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain. 2013;14(12):1539-1552. https://doi.org/10.1016/j.jpain.2013.08.007
Parmelee PA, Tighe CA, Dautovich ND. Sleep disturbance in osteoarthritis: linkages with pain, disability, and depressive symptoms. Arthritis Care Res (Hoboken). 2015;67(3):358-365. https://doi.org/10.1002/acr.22459
Bahouq H, Allali F, Rkain H, et al. Prevalence and severity of insomnia in chronic low back pain patients. Rheumatol Int. 2013;33(5):1277-1281. https://doi.org/10.1007/s00296-012-2550-x
Alsaadi SM, McAuley JH, Hush JM, Maher CG. Prevalence of sleep disturbance in patients with low back pain. Eur Spine J. 2011;20(5):737-743. https://doi.org/10.1007/s00586-010-1661-x
Kim SH, Sun JM, Yoon KB, et al. Risk factors associated with clinical insomnia in chronic low back pain: a retrospective analysis in a university hospital in Korea. Korean J Pain. 2015;28(2):137-143. https://doi.org/10.3344/kjp.2015.28.2.137
Kelly GA, Blake C, Power CK, et al. The association between chronic low back pain and sleep: a systematic review. Clin J Pain. 2011;27(2):169-181. https://doi.org/10.1097/AJP.0b013e3181f3bdd5
Purushothaman B, Singh A, Lingutla K, et al. Prevalence of insomnia in patients with chronic back pain. J Orthop Surg (Hong Kong). 2013;21(1):68-70. https://doi.org/10.1177/230949901302100118
Tang NK, Wright KJ, Salkovskis PM. Prevalence and correlates of clinical insomnia co-occurring with chronic back pain. J Sleep Res. 2007;16(1):85-95. https://doi.org/10.1111/j.1365-2869.2007.00571.x
Marin R, Cyhan T, Miklos W. Sleep disturbance in patients with chronic low back pain. Am J Phys Med Rehabil. 2006;85(5):430-435. https://doi.org/10.1097/01.phm.0000214259.06380.79
Gore M, Sadosky A, Stacey BR, et al. The burden of chronic low back pain: clinical comorbidities, treatment patterns, and health care costs in usual care settings. Spine (Phila Pa 1976). 2012;37(11):668-677. https://doi.org/10.1097/BRS.0b013e318241e5de
Raymond I, Nielsen TA, Lavigne G, et al. Quality of sleep and its daily relationship to pain intensity in hospitalized adult burn patients. Pain. 2001;92(3):381-388. https://doi.org/10.1016/S0304-3959(01)00282-2
Karateev AE, Nasonov EL, Ivashkin VT, et al. Rational use of nonsteroidal anti-inflammatory drugs. Clinical guidelines. Rheumatology Science and Practice. 2018;56:1-29. (In Russ.). https://doi.org/10.14412/1995-4484-2018-1-29
Teutsch G, Mahler DL, Brown CR, et al. Hypnotic efficacy of diphenhydramine, methapyrilene, and pentobarbital. Clin Pharmacol Ther. 1975;17(2):195-201. https://doi.org/10.1002/cpt1975172195
Rickels K, Morris RJ, Newman H, et al. Diphenhydramine in insomniac family practice patients: a double-blind study. J Clin Pharmacol. 1983;23(5-6):234-242. https://doi.org/10.1002/j.1552-4604.1983.tb02730.x
Glass JR, Sproule BA, Herrmann N, Busto UE. Effects of 2-week treatment with temazepam and diphenhydramine in elderly insomniacs: a randomized, placebo-controlled trial. J Clin Psychopharmacol. 2008;28(2):182-188.
Morin CM, Koetter U, Bastien C, et al. Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep. 2005;28(11):1465-1471.
Poluektov MG, Buzunov RV, Averbukh VM, et al. Project of clinical recommendations on diagnosis and treatment of chronic insomnia in adults. Consilium Medicum. Neurology and Rheumatology. 2016;2:41-51.
Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545.
Arterial’naia gipertenziia u vzroslykh. Klinicheskie rekomendatsii. Ministerstvo zdravookhraneniia Rossiiskoi Federatsii, 2020. Accessed: 30.11.22.(In Russ.). https://sudact.ru/law/klinicheskie-rekomendatsii-arterialnaia-gipertenziia-u-vzroslykh-utv/klinicheskie-rekomendatsii/
Buysse DJ, Reynolds CF 3rd, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193-213.
Levin YaI, Kovrov GV, Poluektov MG. Insomnia: modern diagnostic and therapeutic approaches. M.: Eidos Media; 2005. (In Russ.).
Akulova AI, Gaydukova IZ, Rebrov AP. validation of the EQ-5D-5L version In Russia. Rheumatology Science and Practice. 2018;56(3):351-355. (In Russ.). https://doi.org/10.14412/1995-4484-2018-351-355
Golovacheva VA, Golovacheva AA, Fateyeva TG. Clinical principles for the diagnosis and treatment of musculoskeletal (non-specific) lower back pain. Nevrologiya, neiropsikhiatriya, psikhosomatika. 2021;13(3):107-112. (In Russ.). https://doi.org/10.14412/2074-2711-2021-3-107-112
Advil PM Summary Basis of Approval — Medical Review. FDA, 21 December 2005. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021393s000_Advil_PM_MedR.pdf
Aleve PM Summary Basis of Approval — Medical Review. FDA, 20 January 2014. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205352Orig1s000MedR.pdf
Cooper S, Laurora I, Wang Y, et al. Efficacy and tolerability studies evaluating a sleep aid and analgesic combination of naproxen sodium and diphenhydramine in the dental impaction pain model in subjects with induced transient insomnia. Int J Clin Pract. 2015;69(10):1149-1158. https://doi.org/10.1111/ijcp.12669
Kiersch TA, Halladay SC, Hormel PC. A single-dose, double-blind comparison of naproxen sodium, acetaminophen, and placebo in postoperative dental pain. Clin Ther. 1994;16(3):394-404.
Bjørnsson GA, Haanaes HR, Skoglund LA. Naproxen 500 mg bid versus acetaminophen 1000 mg qid: effect on swelling and other acute postoperative events after bilateral third molar surgery. J Clin Pharmacol. 2003;43(8):849-858. https://doi.org/10.1177/0091270003255361

Close metadata