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

Illeez, Ozge Gulsum; Oktay, Kubra Neslihan Kurt; Aktas, Ilknur; Ozkan, Feyza Unlu; Nazligül, Tuba; Begoglu, Feyza Akan; Kaysin, Meryem Yilmaz; Atici, Arzu; Akpinar, Pinar

doi:10.1590/1806-9282.20211047

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Original Article • Rev. Assoc. Med. Bras. 68 (3) • Mar 2022 • https://doi.org/10.1590/1806-9282.20211047 copy

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

Authorship SCIMAGO INSTITUTIONS RANKINGS

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

Parameters	Duloxetine	Pregabalin	p^* * Mann–Whitney U test;	Post hoc 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.	Duloxetine	Pregabalin
Parameters	(n=30) Mean±SD Median (min–max)	(n=30) Mean±SD Median (min–max)	p^* * Mann–Whitney U test;		Duloxetine	Pregabalin
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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	p<0.0001	p<0.0001

Parameters	Duloxetine	Pregabalin	p^* * Mann–Whitney U test;	Post hoc 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.	Duloxetine	Pregabalin
Parameters	(n=30) Mean±SD	(n=30) Mean±SD	p^* * Mann–Whitney U test;		Duloxetine	Pregabalin
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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	p<0.0001	p<0.0001

Parameters	Duloxetine	Pregabalin	p^* * Mann–Whitney U test;	Post hoc test^† † Dunn's multiple comparisons test with Bonferroni correction. Bold indicates statistically significant values. BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; NS: nonsignificant.	Duloxetine	Pregabalin
Parameters	(n=30) Mean+SD	(n=30) Mean+SD	p^* * Mann–Whitney U test;		Duloxetine	Pregabalin
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 ^ Friedman test.	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 ^ Friedman test.	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 ^ Friedman test.	p<0.0001	p<0.0001

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[1] *Corresponding author: ozgeilleez@hotmail.com