NOVEMA® NIGHT (diphenhydramine + naproxen) in patients with pain and insomnia: results of a multicenter non-interventional observational study

Pain and sleep disorders are interrelated problems that significantly affect patients’ quality of life (QoL) and daily functioning.

Objective: to evaluate the efficacy and safety of the use of the combination of diphenhydramine + naproxen (NOVEMA® NIGHT) in patients with acute pain syndrome or exacerbation of chronic pain syndrome and sleep disorders.

Material and methods. The study included 4365 outpatients with acute pain (musculoskeletal pain, post-traumatic pain, headache) and sleep disorders who took naproxen 275 mg, 1 tablet in the morning and diphenhydramine 25 mg + naproxen 220 mg (NOVEMA® NIGHT) for 5 days before bedtime. Pain intensity, using a visual analogue scale (VAS), and sleep disorders were assessed before and after treatment; QoL was assessed after treatment using a five-point scale.

Results. During treatment, a reduction or complete regression of pain was observed in 92% of cases (60 [50; 61] points on the VAS before treatment versus 10 [0; 20] after treatment; p<0.0001) and normalisation of sleep in most patients: faster falling asleep – in 81% (χ²=9650.2; p<0.0001), an increase in total sleep duration – in 75.5% (χ²=7351.2; p<0.0001), a decrease in the number of nocturnal awakenings – in 84% of patients (χ²=10,568; p<0.0001). At the end of treatment course, the majority of patients rated their quality of life as 4 out of 5 possible points (4 [4; 5]): 41% of patients – “high quality of life”; 48% – “above average”; 11% – “average”; 0.09% – “below average”). None of the patients had a low QoL. The therapy was well tolerated and no patient discontinued treatment due to adverse events (AEs).

Conclusion. Short-term treatment (5 days) with naproxen 275 mg and a combination of diphenhydramine 25 mg + naproxen 220 mg (NOVEMA® NIGHT) at bedtime effectively reduces the pain syndrome associated with insomnia. This therapy significantly improves patients’ QoL and has a low risk of AEs, so that we can recommend NOVEMA® NIGHT as an additional analgesic for patients with concomitant sleep disorders.

1. Poluektov MG, Golovatyuk AO. Sleep disorders in acute and chronic pain. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2021;13(3):125-30. doi: 10.14412/2074-2711-2021-3-125-130 (In Russ.).

2. Harrison L, Wilson S, Heron J, et al. Exploring the associations shared by mood, pain-related attention and pain outcomes related to sleep disturbance in a chronic pain sample. Psychol Health. 2016 May;31(5):565-77. doi: 10.1080/08870446.2015.1124106. Epub 2016 Jan 2.

3. Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain. 2013 Dec;14(12):1539-52. doi: 10.1016/j.jpain.2013.08.007

4. Selvanathan J, Tang NKY, Peng PWH, Chung F. Sleep and pain: relationship, mechanisms, and managing sleep disturbance in the chronic pain population. Int Anesthesiol Clin. 2022 Apr 1;60(2):27-34. doi: 10.1097/AIA.0000000000000346

5. Sun Y, Laksono I, Selvanathan J, et al. Prevalence of sleep disturbances in patients with chronic non-cancer pain: A systematic review and meta-analysis. Sleep Med Rev. 2021 Jun;57:101467. doi: 10.1016/j.smrv.2021.101467. Epub 2021 Mar 11.

6. Cheatle MD, Foster S, Pinkett A, et al. Assessing and Managing Sleep Disturbance in Patients with Chronic Pain. Anesthesiol Clin. 2016 Jun;34(2):379-93. doi: 10.1016/j.anclin.2016.01.007

7. NOVEMA NIGHT – instructions for use. Available at: https://novema.ru/instructions/instruction-novemanight/?ysclid=lnlxkc55ac719946860 (In Russ.).

8. Azimova JE, Barantsevich ER, Davydov OS, et al. Expert consensus results. The role of the fixed combination naproxen/diphenhydramine, NOVEMA NIGHT, in the treatment of patients with pain accompanied by sleep disorders. Rossiiskii zhurnal boli = Russian Journal of Pain. 2022;20(4):71-4. doi: 10.17116/pain20222004171 (In Russ.).

9. Levin OS, Skoromets AA, Tabeeva GR, et al. The efficacy and safety of naproxen in the treatment of nonspecific lumbalgia: the results of an open multi-center study (NEST). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2019;119(5):27-31. doi: 10.17116/jnevro201911905127 (In Russ.)

10. Karateev AE. Naproxen: A universal analgesic with a minimal risk of cardiovascular events. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2016;10(2):70-7. doi: 10.14412/1996-7012-2016-2-70-77 (In Russ.).

11. Varas-Lorenzo C, Riera-Guardia N, Calingaert B, et al. Myocardial infarction and individual nonsteroidal anti-inflammatory drugs meta-analysis of observational studies. Pharmacoepidemiol Drug Saf. 2013 Jun;22(6):559-70. doi: 10.1002/pds.3437

12. Karateev AE. A patient with osteoarthritis out of a doctor's field of vision: how should joint pain be controlled within the concept of responsible self-treatment? Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(2S):52-61. doi: 10.14412/2074-2711-2019-2S-52-61 (In Russ.).

13. Fathi M, Zare MA, Bahmani HR, Zehtabchi S. Comparison of oral oxycodone and naproxen in soft tissue injury pain control: a double-blind randomized clinical trial. Am J Emerg Med. 2015 Sep;33(9):1205-8. doi: 10.1016/j.ajem.2015.05.021. Epub 2015 May 29.

14. Friedman BW, Dym AA, Davitt M, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015 Oct 20;314(15):1572-80. doi: 10.1001/jama.2015.13043

15. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011 Jan 11;342:c7086. doi: 10.1136/bmj.c7086

16. Barantsevich ER, Karakulova YuV, Baranova NS, Morzhukhina MV. Treatment of sleep disturbances associated with chronic non-specific low back pain: results of prospective randomized multicenter open-label clinical trial. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2022;122(12):85-94. doi: 10.17116/jnevro202212212185 (In Russ.).

17. 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):1149-58. doi: 10.1111/ijcp.12669

18. Sleep quality questionnaire. Available from: https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Fageremeev.ru%2Fson%2520(metod).doc%3Fyscli d%3Dlnlxxc2de0827244570&wdOrigin=BROWSELINK (In Russ.).

19. Afolalu EF, Ramlee F, Tang NKY. Effects of sleep changes on pain-related health outcomes in the general population: A systematic review of longitudinal studies with exploratory meta-analysis. Sleep Med Rev. 2018;39:82-97. doi: 10.1016/j.smrv.2017.08.001. Epub 2017 Aug 18.

20. Haack M, Simpson N, Sethna N, et al. Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology. 2020;45(1):205-16. doi: 10.1038/s41386-0190439-z

21. Parfenov VA, Yakhno NN, Kukushkin ML, et al. Non-specificneckpain (cervicalgia). Guidelines of the Russian Society for the Study of Pain (RSSP). Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2023;15(5):4-12. doi: 10.14412/2074-27112023-5-4-12 (In Russ.).

22. Coxib and traditional NSAID Trialists' (CNT) Collaboration; Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769-79. doi: 10.1016/S0140-6736(13)60900-9. Epub 2013 May 30.

23. Asghar W, Jamali F. The effect of COX-2selective meloxicam on the myocardial, vascular and renal risks: a systematic review. Inflammopharmacology. 2015 Feb;23(1):1-16. doi: 10.1007/s10787-014-0225-9. Epub 2014 Dec 17.

24. Almond SM, Warren MJ, Shealy KM, et al. A Systematic Review of the Efficacy and Safety of Over-the-Counter Medications Used in Older People for the Treatment of Primary insomnia. Sr Care Pharm. 2021 Feb 1;36(2):8392. doi: 10.4140/TCP.n.2021.83