Comparison of the effects of duloxetine and pregabalin on pain and associated factors in patients with knee osteoarthritis

SUMMARY

OBJECTIVES:

This study aimed to investigate the effects of duloxetine and pregabalin primarily on pain and functional status in patients with knee osteoarthritis and secondarily on quality of life, depression, anxiety, and sleep disturbance.

METHODS:

A total of 66 patients with knee osteoarthritis were randomized to use duloxetine or pregabalin. Patients were evaluated by Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36, Beck Depression Inventory, Beck Anxiety Inventory, and Pittsburg Sleep Quality Index before the treatment and after 4 and 12 weeks of treatment.

RESULTS:

Improvements occurred in Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36 (with an exception of the mental health subgroup scores in duloxetine-treated group), Beck Depression Inventory, and Beck Anxiety Inventory scores in both groups from 4 weeks after baseline. Pittsburg Sleep Quality Index total scores and SF-36 mental health subgroup scores started to improve on the 4th and 12th weeks in pregabalin- and duloxetine-treated groups, respectively.

CONCLUSION:

Osteoarthritis pain, a complex outcome with nociceptive and neuropathic components, leads to central sensitization in a chronic phase. Using centrally acting drugs in the control of pain and associated symptoms would increase the probability of treatment success.

KEYWORDS:
Duloxetine hydrochloride; Knee; Osteoarthritis; Pain; Pregabalin

INTRODUCTION

Osteoarthritis (OA) is a chronic, degenerative disease frequently seen in the middle-aged and elderly people. Knee OA is a particularly common type of OA and a major cause of disability¹. OA pain is a mixed type of pain involving both nociceptive and neuropathic components. Pain is the most pronounced symptom in knee OA, being initially associated with activity and becoming continuous and severe as the disease progresses. This is thought to be due to the development of central sensitization. Central sensitization is a pain processing abnormality occurring in chronic pain due to persistent activation of the spinal and supraspinal neurons. This process may also cause comorbid conditions such as fear, anxiety, depression, and sleep disorders²,³. Central sensitization in knee OA has particularly been shown in patients describing severe pain but without radiological findings indicating the same pain severity⁴,⁵.

Because of the mechanism involved in central sensitization in OA, the use of therapeutic agents that affect the central pain pathways may be required. Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, is found to be effective in the treatment of chronic pain because of its antidepressant and anxiolytic properties. Duloxetine has been reported to be effective in the treatment of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain⁶. Pregabalin suppresses the release of excitatory neurotransmitters by combining with alpha-2-delta subunits of voltage-dependent calcium channels in the central nervous system. It also exhibits positive effects on neuropathic pain-related sleep disturbance, depression, and anxiety. Therapeutic guidelines recommend gabapentinoids (pregabalin-gabapentin) as the first choice medications in the treatment of neuropathic pain⁷.

This study was intended to compare the effects of duloxetine and pregabalin on pain and function in patients with OA. The secondary purpose of the study was to examine the effects of these central-acting drugs on anxiety, depression, and sleep disturbance frequently seen during chronic pain and on the quality-of-life parameters. To the best of our knowledge, no previous studies have compared the efficacy of pregabalin and duloxetine in knee OA.

METHODS

This prospective, randomized clinical study was performed between October 2016 and December 2020. The study was approved by the Institutional Ethics Committee (FSMEAH-KAEK 9.06.2016/50), and informed consent was obtained from all patients before commencement. Inclusion criteria were age over 40, diagnosis with OA based on the American College of Rheumatology primary knee OA criteria; posterior–anterior X-ray examination showing grades 2–3 knee OA according to the Kellgren and Lawrence Radiological Classification System; a VAS score and a DN4 scale value of 4 or more; and more than 14 painful days a month for at least the past 3 months. Exclusion criteria were body mass index (BMI) higher than 40; the presence of diabetes mellitus, congestive heart failure, cancer, fibromyalgia, inflammatory arthropathy, or autoimmune disease; receipt of invasive treatment with a diagnosis of OA in the past 3 months; being nonambulatory or using assistant devices for walking; and the presence of psychiatric or neurological disease. Notably, 66 patients whose eligibility was confirmed were randomized to one of the two groups, and 3 patients from each group subsequently dropped out from the study; finally, only 60 patients participated in the study. One group was administered 60 mg/day duloxetine HCl, and another group was given 300 mg/day pregabalin, both for 12 weeks. In the duloxetine-treated group, the drug was administered as a single 30 mg dose in the first week and at 60 mg/day from the second week. Patients in the pregabalin-treated group received 75 mg orally twice a day in the first week, followed by 150 mg orally twice a day from the second week. Patient assessments were performed before the treatment and at the 4th and 12th weeks of the treatment. The primary outcome measures were VAS, DN4, and WOMAC, and the secondary outcome measures were BDI, BAI, PSQI, and SF-36. Side effects of the drug were questioned in the patients at the follow-ups.

Statistical evaluation

Data analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 23 software. Frequency and percentage values were calculated for categorical variables, while continuous variables were expressed as mean, standard deviation, median, minimum, and maximum values. Compatibility with a normal distribution of continuous variables was evaluated using the Kolmogorov–Smirnov test. Relationships between categorical variables were determined using the chi-square test. The Mann–Whitney U test was used to compare non-normally distributed variables between two independent groups, and the Friedman test was used for comparisons between more than two groups. Dunn's multiple comparisons test with Bonferroni correction was used for two-way comparisons. Statistical analyses were evaluated at a significance level of 0.05.

RESULTS

No significant difference was determined between the two groups in terms of age, gender, mean duration of disease, Kellgren and Lawrence grade, or initial scores for all the parameters examined. However, BMI was higher in the duloxetine-treated group than that in the pregabalin-treated group (p=0.017). Inter- and intragroup changes in VAS day and night pain, DN4, and WOMAC scores are shown in Table 1. Inter- and intragroup changes in SF-36 and subgroup scores are shown in Table 2. Inter- and intragroup changes in BDI, BAI, and PSQI scores are shown in Table 3.

Table 1
Inter- and intragroup changes in VAS, DN4, and WOMAC scores.

Parameters	Duloxetine	Pregabalin	p*	Post hoc test†	Duloxetine	Pregabalin
	(n=30) Mean±SD Median (min–max)	(n=30) Mean±SD Median (min–max)
VAS daytime 0	6.77±1.43 7 [4–10]	7.03±1.54 7 [5–10]	0.476	0 vs. 4	p<0.0001	p<0.0001
VAS daytime 4	3.4±1.92 3 [0–8]	3.4±1.73 3 [1–8]	0.893	0 vs. 12	p<0.0001	p<0.0001
VAS daytime 12	2.7±2.1 3 [0–8]	2.1±2.12 1 [0–9]	0.179	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
VAS nighttime 0	6.83±1.7 7 [4–10]	6.73±2.53 8 [0–9]	0.647	0 vs. 4	p<0.0001	p<0.0001
VAS nighttime 4	3.57±1.96 3.5 [0–8]	2.97±1.94 3 [0–8]	0.242	0 vs. 12	p<0.0001	p<0.0001
VAS nighttime 12	2.6±2.14 2.5 [0–8]	1.9±2.02 2 [0–9]	0.152	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
DN4-0	5.27±1.6 5 [4–9]	4.9±1.21 4 [4–8]	0.410	0 vs. 4	p<0.0001	p<0.0001
DN4-4	3.03±1.63 3 [0–7]	1.47±1.2 1 [0–5]	p<0.0001	0 vs. 12	p<0.0001	p<0.0001
DN4-12	2.73±1.62 3 [0–7]	1.43±1.28 1 [0–5]	0.001	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
WOMAC 0 pain	13.37±3.83	12.47±4.36	0.377	0 vs. 4	p<0.0001	p<0.0001
WOMAC 4 pain	8.67±4.36	6.53±3.72	0.038	0 vs. 12	p<0.0001	p<0.0001
WOMAC 12 pain	7.2±5.61	4.2±4.29	0.020	4 vs. 12	NS	0.024
p **	p<0.0001	p<0.0001
WOMAC 0 stiffness	5±2.27	4.03±2.16	0.101	0 vs. 4	p<0.0001	p<0.0001
WOMAC 4 stiffness	3.33±2.2	2±1.82	0.016	0 vs. 12	p<0.0001	0.001
WOMAC 12 stiffness	3±2.17	1.37±1.69	0.002	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
WOMAC 0 function	40.6±14.66	38.1±14.56	0.662	0 vs. 4	p<0.0001	p<0.0001
WOMAC 4 function	26.2±13.58	21.03±14.3	0.141	0 vs. 12	p<0.0001	p<0.0001
WOMAC 12 function	22.93±17.08	14.5±14.98	0.043	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
WOMAC 0 total	60.62±19.17	56.52±20.3	0.473	0 vs. 4	p<0.0001	p<0.0001
WOMAC 4 total	39.3±19.47	30.9±19.59	0.109	0 vs. 12	p<0.0001	p<0.0001
WOMAC 12 total	34.02±23.81	20.9±21.28	0.022	4 vs. 12	NS	0.029
p **	p<0.0001	p<0.0001

• ^*
  Mann–Whitney U test;
• ^**
  Friedman test.
• ^†
  Dunn's multiple comparisons test with Bonferroni correction. Min: minimum; Max: maximum; SD: standard deviation; VAS: Visual Analog Scale; NS: nonsignificant. Bold indicates statistically significant values.

Table 2
Inter- and intragroup SF-36 and sub-parameter changes.

Parameters	Duloxetine	Pregabalin	p*	Post hoc test†	Duloxetine	Pregabalin
	(n=30) Mean±SD	(n=30) Mean±SD
SF-36 PF 0	43.17±17.79	41.67±21.15	0.917	0 vs. 4	p=0.001	p=0.001
SF-36 PF 4	64±22.22	64±20.98	0.870	0 vs. 12	p<0.0001	p<0.0001
SF-36 PF 12	71.08±21.69	76±22.61	0.237	4 vs. 12	NS	0.035
p **	p<0.0001	p<0.0001
SF-36 PRF 0	20.22±35.97	20.83±34.79	0.844	0 vs. 4	0.002	0.002
SF-36 PRF 4	62.21±40.75	69.17±44.37	0.414	0 vs. 12	p<0.0001	p<0.0001
SF-36 PRF 12	68.44±39.31	83.33±33.69	0.112	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
SF-36 ERF 0	38.87±35.1	31.09±28.93	0.450	0 vs. 4	p<0.0001	p<0.0001
SF-36 ERF 4	69.96±25.31	71.1±37.89	0.463	0 vs. 12	0.007	0.011
SF-36 ERF 12	80.53±26.31	85.55±29.93	0.184	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
SF-36 V 0	40.11±22.39	36.73±24.34	0.276	0 vs. 4	p<0.0001	p<0.0001
SF-36 V 4	48±22.54	55.33±22.7	0.194	0 vs. 12	0.014	0.014
SF-36 V 12	58.27±21.55	64±18.82	0.357	4 vs. 12	0.024	NS
p **	p<0.0001	p<0.0001
SF-36 MH0	49.5±23.49	50.8±24.14	0.716	0 vs. 4	NS	p<0.0001
SF-36 MH 4	55.83±17.53	66.4±18.98	0.014	0 vs. 12	0.006	0.002
SF-36 MH 12	61.23±21.4	71.67±14.73	0.055	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
SF-36SRF 0	56.85±24.19	49.58±26.16	0.187	0 vs. 4	0.020	0.001
SF-36 SRF 4	69.5±25.15	72.92±21.3	0.799	0 vs. 12	p<0.0001	p<0.0001
SF-36 SRF 12	75.03±22.12	78.75±17.1	0.689	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
SF-36 BP 0	31.33±18.47	23.17±17.37	0.061	0 vs. 4	p<0.0001	p<0.0001
SF-36 BP 4	58.42±24.05	62.25±21.79	0.336	0 vs. 12	p<0.0001	p<0.0001
SF-36 BP 12	63.75±29.41	66.83±25.02	0.911	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
SF-36 GHP 0	36.5±20.14	42.1±23.47	0.509	0 vs. 4	p<0.0001	0.002
SF-36 GHP 4	50.23±16.62	59.57±18.02	0.063	0 vs. 12	p<0.0001	p<0.0001
SF-36 GHP 12	56.92±20.59	69.07±14.62	0.022	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001

• ^*
  Mann–Whitney U test;
• ^**
  Friedman test.
• ^†
  Dunn's multiple comparisons test with Bonferroni correction. Bold indicates statistically significant values. SF-36: Short Form-36; PF: physical functioning; PRF: physical role functioning; ERF: emotional role functioning; V: vitality; MH: mental health; SRF: social role functioning; BP: bodily pain; GHP: general health perceptions; SD: standard deviation; VAS: Visual Analog Scale; NS: nonsignificant.

Table 3
Inter- and intragroup changes in BDI, BAI, and Pittsburg scores.

Parameters	Duloxetine	Pregabalin	p*	Post hoc test†	Duloxetine	Pregabalin
	(n=30) Mean+SD	(n=30) Mean+SD
BDI 0	17.2±8.72	16.53±9.21	0.841	0 vs. 4	p<0.001	p<0.017
BDI 4	11.63±7.65	10.47±8.11	0.501	0 vs. 12	p<0.0001	p<0.0001
BDI 12	10.13±7.88	7.83±6.26	0.310	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
BAI 0	17.63±13.63	17.63±9.98	0.594	0 vs. 4	0.002	0.001
BAI 4	13.07±11.23	10.87±7.59	0.706	0 vs. 12	p<0.0001	p<0.0001
BAI 12	11±9.67	7.3±6.18	0.109	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001
Pittsburg total-0	8.93±4.87	11±4.99	0,119	0 vs. 4	NS	0.001
Pittsburg total-4	7.13±5.11	6.93±4.37	0.795	0 vs. 12	0.001	p<0.0001
Pittsburg total-12	6.27±5.09	5.9±3.52	0.522	4 vs. 12	NS	NS
p **	p<0.0001	p<0.0001

• ^*
  Mann–Whitney U test;
• ^**
  Friedman test.
• ^†
  Dunn's multiple comparisons test with Bonferroni correction. Bold indicates statistically significant values. BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; NS: nonsignificant.

Side effects were recorded prospectively throughout the study. A total of 16 side effects were observed in the duloxetine-treated group [i.e., constipation (4), dizziness (4), nausea (2), somnolence (1), peripheral edema (1), fatigue (1), pruritus (1), genitourinary symptoms (1), and diarrhea (1)], and 25 side effects were observed in the pregabalin-treated group [i.e., somnolence (6), constipation (4), dizziness (4), weight gain (3), nausea (2), peripheral edema (2), pruritus (1), skin eruption (1), dry mouth (1), and abdominal distension (1)]. In the duloxetine-treated group, three patients were withdrawn from the study (one patient due to pain persisting at the same level of severity, one patient due to constipation, and one patient due to dizziness). In the pregabalin-treated group, 3 patients were dropped out from the study (one patient due to peripheral edema in the bilateral lower extremities and two patients due to somnolence). Other side effects were not severe enough to prevent patients from continuing treatment.

DISCUSSION

In this study, significant improvement was observed compared with pre-treatment values in all parameters in both drug groups from the fourth week. Two exceptions were that total sleep scores and SF-36 MH scores in the duloxetine-treated group only improved compared with baseline in the 12th week. A significant difference between weeks 4 and 12 was also present in a small number of parameters, functional status, and quality-of-life subscores. A comparison of duloxetine and pregabalin treatment revealed that pregabalin was superior in terms of its effects on the neuropathic component of pain, functional status, and some quality-of-life parameters.

Earlier, OA pain was generally regarded as a peripherally mediated nociceptive pain. However, inflammatory mediators have been shown to modulate both peripheral and central nociceptors following intra-articular release from damaged tissues⁸. Patients with OA are now known to experience varying degrees of both nociceptive and neuropathic pain⁹. Significant scientific evidence also reports a role for central sensitization in OA pain. The presence of central sensitization confuses the clinical picture and makes it less likely to respond to conventional treatments¹⁰. The addition of centrally acting agents to conventional therapies in the treatment of OA has been shown to increase the response to treatment¹¹.

There have been very few studies of the use of pregabalin in knee OA. Rahman et al. described pregabalin as useful against pain resulting from knee OA in an animal model and demonstrated modified physiology of deep dorsal horn wide dynamic range neurons, suggesting an association between heightened neuronal activity and hypersensitive behavioral responses¹². In another study using a lower pregabalin dosage than in this study, patients with knee OA were randomized into groups receiving meloxicam 10 mg, meloxicam 10 mg/day+pregabalin 25 mg/day, and pregabalin 25 mg/day only. Significant improvements were recorded in the meloxicam+pregabalin group in terms of pain and functional status scores, showing that knee OA represents a combination of both nociceptive and neuropathic pain¹¹. In another study, the same number of patients as in this study were randomized into aceclofenac- and aceclofenac+pregabalin-treated groups, and significant improvement in both pain severity and functional status was observed in the combination therapy group compared with the monotherapy group¹³.

There have been more studies investigating the use of duloxetine in knee OA than pregabalin. A meta-analysis of three randomized controlled studies involving a total of 1011 patients reported significant improvement in pain and functional status in patients using 60/120 mg duloxetine following approximately 10–13 weeks of treatment compared with a placebo group. Similar to this study, tolerable levels of side effects such as nausea, fatigue, constipation, hyperhidrosis, somnolence, dizziness, diarrhea, insomnia, and dry mouth were reported in the three studies in that meta-analysis¹⁴. A double-blinded randomized, controlled study of 354 patients reported no change in knee joint movement and x-ray findings in a duloxetine-treated group but observed significant improvement in pain and functional status compared with a control group⁶. Another study of 288 patients with knee OA aged over 65 reported significant improvements in pain, functionality, and geriatric depressions scores in a duloxetine-treated group compared with a placebo group¹⁵. A study comparing the efficacy of pregabalin and duloxetine in patients with hand OA reported that both agents were effective against chronic hand OA pain, with pregabalin being superior to duloxetine. However, in contrast to the findings of this study, neither of the two drugs was reported to produce any improvement in either depression or anxiety scores¹⁶.

Chronic pain developing in association with OA can result in impairment of health-related quality of life and daily activities, and psychological distress, including depression¹⁷ and sleep disturbances¹⁸. The prevalence of depression is estimated to be two to three times higher in patients with OA¹⁹–²⁰. Sarıyıldız et al. reported impairment of sleep quality in patients with knee OA and that this was particularly associated with knee pain, age, depressive symptoms, and radiological grade²¹. Alkan et al. reported lower SF-36 scores among patients with OA compared with healthy controls²². In this study, treatment with both duloxetine and pregabalin improved anxiety, depression, and sleep disturbance symptoms, together with the quality of life. Despite not reaching statistical significance, pregabalin was superior to duloxetine in all these parameters, and pregabalin also exhibited its effect on sleep disturbance earlier. Studies examining the effectiveness of pregabalin on anxiety and depression have reported inconsistent findings regarding pain, but similar results in terms of its effect on sleep. Gilron et al. reported that pregabalin yielded a small but significant difference in sleep interference, anxiety, and depression scores²³. This study has some limitations. The first limitation is the absence of a control group. Although we knew that using a placebo group would make our study more valuable, we did not use a placebo group because we thought that the quality of life of the patients might be affected by this process. The second one is the short follow-up period, since more informative results might have been yielded by a longer follow-up period. The third limitation is that BMI was higher in the duloxetine group than that in the pregabalin group. This may partially account for the superiority of pregabalin in terms of knee functionality.

CONCLUSIONS

Pain in OA is a complex event involving both nociceptive and neuropathic components. According to the results of our study, both duloxetine and pregabalin are effective in reducing mixed type of pain and improving functions. These agents also are useful against depression, anxiety, and sleep disorder, which frequently accompany the chronic process, and can thus contribute to an improvement of the patient's quality of life.

• Funding: none.
• ETHICAL APPROVAL
  The study was approved by the Institutional Ethics Committee (FSMEAH-KAEK 9.06.2016/50). Clinical trial ID: NCT04532684, retrospectively registered 25.01.2021.

REFERENCES

• ¹
  Lespasio MJ, Piuzzi NS, Husni ME, Muschler GF, Guarino A, Mont MA. Knee osteoarthritis: a primer. Perm J. 2017;21:16-183. https://doi.org/10.7812/TPP/16-183
  » https://doi.org/10.7812/TPP/16-183
• ²
  Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1-32. https://doi.org/10.1146/annurev.neuro.051508.135531
  » https://doi.org/10.1146/annurev.neuro.051508.135531
• ³
  Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895-926. https://doi.org/10.1016/j.jpain.2009.06.012
  » https://doi.org/10.1016/j.jpain.2009.06.012
• ⁴
  Finan PH, Buenaver LF, Bounds SC, Hussain S, Park RJ, Haque UJ, et al. Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis Rheum. 2013;65(2): 363-–72. https://doi.org/10.1002/art.34646
  » https://doi.org/10.1002/art.34646
• ⁵
  Niissalo S, Hukkanen M, Imai S, Törnwall J, Konttinen YT. Neuropeptides in experimental and degenerative arthritis. Ann N Y Acad Sci. 2002;966:384-99. https://doi.org/10.1111/j.1749-6632.2002.tb04239.x
  » https://doi.org/10.1111/j.1749-6632.2002.tb04239.x
• ⁶
  Uchio Y, Enomoto H, Alev L, Kato Y, Ishihara H, Tsuji T, et al. A randomized, double-blind, placebo-controlled Phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. J Pain Res. 2018;11:809-21. https://doi.org/10.2147/JPR.S164128
  » https://doi.org/10.2147/JPR.S164128
• ⁷
  Sumitani M, Sakai T, Matsuda Y, Abe H, Yamaguchi S, Hosokawa T, et al. Executive summary of the Clinical Guidelines of Pharmacotherapy for Neuropathic Pain: second edition by the Japanese Society of Pain Clinicians. J Anesth. 2018;32(3):463-78. https://doi.org/10.1007/s00540-018-2501-0
  » https://doi.org/10.1007/s00540-018-2501-0
• ⁸
  Hochman JR, Gagliese L, Davis AM, Hawker GA. Neuropathic pain symptoms in a community knee OA cohort. Osteoarthritis Cartilage. 2011;19(6):647-54. https://doi.org/10.1016/j.joca.2011.03.007
  » https://doi.org/10.1016/j.joca.2011.03.007
• ⁹
  Roubille C, Raynauld JP, Abram F, Paiement P, Dorais M, Delorme P, et al. The presence of meniscal lesions is a strong predictor of neuropathic pain in symptomatic knee osteoarthritis: a cross-sectional pilot study. Arthritis Res Ther. 2014;16(6):507. https://doi.org/10.1186/s13075-014-0507-z
  » https://doi.org/10.1186/s13075-014-0507-z
• ¹⁰
  Lluch Girbés E, Nijs J, Torres-Cueco R, López Cubas C. Pain treatment for patients with osteoarthritis and central sensitization. Phys Ther. 2013;93(6):842-51. https://doi.org/10.2522/ptj.20120253
  » https://doi.org/10.2522/ptj.20120253
• ¹¹
  Ohtori S, Inoue G, Orita S, Takaso M, Eguchi Y, Ochiai N, et al. Efficacy of combination of meloxicam and pregabalin for pain in knee osteoarthritis. Yonsei Med J. 2013;54(5):1253-8. https://doi.org/10.3349/ymj.2013.54.5.1253
  » https://doi.org/10.3349/ymj.2013.54.5.1253
• ¹²
  Rahman W, Bauer CS, Bannister K, Vonsy JL, Dolphin AC, Dickenson AH. Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain. Mol Pain. 2009;5:45. https://doi.org/10.1186/1744-8069-5-45
  » https://doi.org/10.1186/1744-8069-5-45
• ¹³
  Filatova ES, Turovskaya EF, Alekseeva LI. Evaluation of the efficacy of pregabalin in the therapy of chronic pain in patients with knee osteoarthritis. Ter Arkh. 2017;89(12):81-5. https://doi.org/10.17116/terarkh2017891281-85
  » https://doi.org/10.17116/terarkh2017891281-85
• ¹⁴
  Wang ZY, Shi SY, Li SJ, Chen F, Chen H, Lin HZ, et al. Efficacy and safety of duloxetine on osteoarthritis knee pain: a meta-analysis of randomized controlled trials. Pain Med. 2015;16(7):1373-85. https://doi.org/10.1111/pme.12800
  » https://doi.org/10.1111/pme.12800
• ¹⁵
  Abou-Raya S, Abou-Raya A, Helmii M. Duloxetine for the management of pain in older adults with knee osteoarthritis: randomised placebo-controlled trial. Age Ageing. 2012;41(5):646-52. https://doi.org/10.1093/ageing/afs072
  » https://doi.org/10.1093/ageing/afs072
• ¹⁶
  Sofat N, Harrison A, Russell MD, Ayis S, Kiely PD, Baker EH, et al. The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis. J Pain Res. 2017;10:2437-49. https://doi.org/10.2147/JPR.S14764
  » https://doi.org/10.2147/JPR.S14764
• ¹⁷
  Axford J, Butt A, Heron C, Hammond J, Morgan J, Alavi A, et al. Prevalence of anxiety and depression in osteoarthritis: use of the Hospital Anxiety and Depression Scale as a screening tool. Clin Rheumatol. 2010;29(11):1277-83. https://doi.org/10.1007/s10067-010-1547-7
  » https://doi.org/10.1007/s10067-010-1547-7
• ¹⁸
  Sasaki E, Tsuda E, Yamamoto Y, Maeda S, Inoue R, Chiba D, et al. Nocturnal knee pain increases with the severity of knee osteoarthritis, disturbing patient sleep quality. Arthritis Care Res (Hoboken). 2014;66(7):1027-32. https://doi.org/10.1002/acr.22258
  » https://doi.org/10.1002/acr.22258
• ¹⁹
  Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med. 2003;163(20):2433-45. https://doi.org/10.1001/archinte.163.20.2433
  » https://doi.org/10.1001/archinte.163.20.2433
• ²⁰
  He Y, Zhang M, Lin EH, Bruffaerts R, Posada-Villa J, Angermeyer MC, et al. Mental disorders among persons with arthritis: results from the World Mental Health Surveys. Psychol Med. 2008;38(11):1639-50. https://doi.org/10.1017/S0033291707002474
  » https://doi.org/10.1017/S0033291707002474
• ²¹
  Sarıyıldız MA, Batmaz İ, Kaya MC, Bozkurt M, Okçu M, Yıldız M, et al. Association of the sleep quality with pain, radiological damage, functional status and depressive symptoms in patients with knee osteoarthritis. J Clin Exp Invest. 2013;4(2):189-94. https://doi.org/10.5799/ahinjs.01.2013.02.0263
  » https://doi.org/10.5799/ahinjs.01.2013.02.0263
• ²²
  Alkan BM, Fidan F, Tosun A, Ardıçoğlu O. Quality of life and self-reported disability in patients with knee osteoarthritis. Mod Rheumatol. 2014;24(1):166-71. https://doi.org/10.3109/14397595.2013.854046
  » https://doi.org/10.3109/14397595.2013.854046
• ²³
  Gilron I, Wajsbrot D, Therrien F, Lemay J. Pregabalin for peripheral neuropathic pain: a multicenter, enriched enrollment randomized withdrawal placebo-controlled trial. Clin J Pain. 2011;27(3):185-93. https://doi.org/10.1097/AJP.0b013e3181fe13f6
  » https://doi.org/10.1097/AJP.0b013e3181fe13f6

Publication Dates

• Publication in this collection
  15 Apr 2022
• Date of issue
  Mar 2022

History

• Received
  17 Nov 2021
• Accepted
  07 Jan 2022