Table 5.

Studies examining the relationship between depression and knee pain

Author (year)	Study design	Assessment of depression	Assessment of pain pain/OA	Results	Conclusion	Quality score
Creamer (1999- Baltimore study)	Cross-sectional	Arthritis Impact Measurement Scales (AIMS) Questionnaire (Depression subscale)	Pain on most days for at least one month (National Health and Nutrition Examination Survey (NHANES-1))	Pain reporting was not related to depression (statistics not provided).	Depression was not associated with knee pain.	55
				Depression scores were higher in subjects reporting ‘ever’ pain in the presence of normal radiographs than in those without reported knee pain (1.70 ± 0.27 versus 1.16 ± 0.09), but this was not statistically significant (P= 0.06).
Creamer (1999)	Cross-sectional	Centre for Epidemiological Studies Depression Scale (CES-D)	Pain Severity	Unadjusted Correlations: MPQ: r= 0.31 (p < 0.05).	There was no association between depression and pain severity after adjustment.	55
			(WOMAC, Visual Analogue Scale,	VAS: r= 0.19 (NS)
			McGill Pain Questionnaire (MPQ))	WOMAC: r= 0.15 (NS)
				In the stepwise regression models after adjustment, depression did not remain in the model.
Salaffi (1991)	Cross-sectional	Zung Depression Inventory	Pain	Stepwise multiple regression:	Depression was found to be associated with the pain experience.	45
			(McGill Pain Questionnaire (MPQ), Visual Analogue Scale (VAS))
				MPQ: R= 0.41; t= 2.99; p < 0.01
				VAS R= 0.39; t= 2.77; p < 0.01
van Baar (1998)	Cross-sectional	IRGL Questionnaire	Severity of pain: Visual Analogue Scale	Bivariate Correlation:	Depression was not associated with knee pain.	64
				Knee pain: r= 0.28 p ≤ 0.01
				Regression Analysis: NS (not remain in the model)
Wright (2008)	Cross-sectional	CES-D	WOMAC pain scale	WOMAC: mean= 17.76 ± 14.47	There was an association between knee pain and depressive symptoms.	82
		Psychological Disability subscale of AIMS
				Depressive Sx: mean= 1.80 ± 2.79
				Neuroticism: mean= 2.26 ± 0.59
				Negative affect: mean= 1.67 ± 0.51
				Correlation between pain and depressive Sx: r= 0.21; p < 0.01
				Correlation between pain and negative affect: r= 0.15; p < 0.05
Pells (2008)	Cross-sectional	Psychological Disability subscale of AIMS	AIMS	Correlation between psychosocial disability and AIMS pain scale: r= 0.24; p < 0.01.	Pain did not demonstrate an association with psychological disability.	64
				Multiple regression: NS
Peat (2009)	Nested case-controlled	Hospital Anxiety and Depression Scale	Characteristic pain intensity: Chronic Pain Grade	Mean difference (95% CI) of depression between cases and controls at 18 months: 2.2 (1.2 to 3.1)	Substantial deterioration of knee pain is accompanied by an increase in depressive symptoms.	79
			Pain extent: areas of pain experienced in previous month shaded on whole-body manikin
				Cases were subjects who had mild knee pain at study entry and become severe at 18 months follow up.
			Night pain: single item on WOMAC	Controls were subjects who still had mild knee pain at 18 months follow up and were selected from similar cohort as cases).
Riddle (2011)	Longitudinal Cohort Study	20-item CES-D	Knee Pain: WOMAC pain scale	dichotomised CES-D score (≥16)	Baseline depression is the most consistent psychological predictor of yearly worsening of pain. Association exists after adjusting for confounding variables.	92
			Disability: WOMAC disability scale	Univariate analysis: WOMAC Pain: Estimate (95% CI)= 0.36 (0.16 to 0.56); p < 0.001
				Multivariate analysis: WOMAC Pain: Estimate (95% CI)= 0.59 (0.18 to 1.01); p= 0.005
Chappell	Randomised Controlled Trial(RCT) investigating the effect of antidepressant (Duloxetine) on knee OA	Beck Depression Inventory-II (BDI-II) Hospital Anxiety and Depression Scale anxiety subscale (HADS-A)	Knee Pain: Brief Pain Inventory (BPI); WOMAC pain and stiffness subscales Perceived improvement: Clinical Global Impressions of Severity (CGI-S)	Mean change in pain score from baseline (at 13 weeks)	Treatment with duloxetine 60 to 120 mg was associated with significant pain reduction in patients with pain due to knee OA.	8*
(USA, 2011)
				BPI average pain (% response)
				≥30%= 65.3 (antidepressant group= I) & 44.1 (placebo= C); p ≤ 0.001
				WOMAC: -13.74 (I) -17.51 (C); p ≤0.05
				CGI-S: -0.40 (I) & -0.70(C); p ≤ 0.01
Chappell	RCT investigating the effect of antidepressant (Duloxetine) on knee OA	Beck Depression Inventory-II	Knee Pain: Weekly 24-h worst pain; WOMAC pain subscale	Mean change (SD) in pain score from baseline (at 13 weeks)	Duloxetine demonstrated statistically significant pain reduction compared with placebo.	9*
(USA, 2009)
		Hospital Anxiety and Depression Scale (HADS)
				BPI-S(Average pain): –2.82 ±0.21(C) –1.85 ± 0.21(C); p < .001
			Severity: BPI-S, Brief Pain Inventory-Severity; CGI-S, Clinical Global Impressions of Severity
				WOMAC: –4.64 ± 0.35 (I)
				−3.24 ± 0.35(C); p= 0.003
				CGI-S: -0.65 ±0.08(I) & –0.29 ± 0.08(C); p= 0.001
Abou-Raya	RCT investigating the effect of antidepressant (Duloxetine) on knee OA	Geriatric depression scale	Knee Pain Visual analogue pain scale; WOMAC pain score	WOMAC pain score	Duloxetine has a dual beneficial effect of improving depression and pain symptoms in older adults with knee OA.	10*
(Egypt, 2012)				(0–20): Mean (SD)
				At baseline: Intervention - 9.1(4.6)
				Placebo - 8.9(5.1); p= 0.44
				At 16 weeks : Intervention - 6.0 (4.1) Placebo - 8.4 (5.4); p= 0.05

NHANES , National Health and Nutritional Examination Survey; PFS , Physical Functioning Score; WOMAC , Western Ontario and McMaster University Osteoarthritis Index; PCI , Pain Coping Inventory; 4DSQ , Four Dimensional Symptom Questionnaire; CES-D , Centre for Epidemiological Studies Depression Scale; QOL , Quality of Life; SF-36 , Short-Form-36 Health Survey; SSS - Social Support Scale; VAS , Visual Analogue Scale; OA , osteoarthritis; K/L scale , Kellgren and Lawrence Atlas of Standard Radiographs of Arthritis; WOMAC , Western Ontario and McMaster University Arthritis Index; MPQ , McGill Pain Questionnaire; AIMS , Arthritis Impact Measurement Scales; ACR , American College of Rheumatology; NA , not available; PFS , Physical Functioning Scale; IRGL , Invloed van Reuma op Gezondheid en Leefwijze (Dutch version of the Arthritis Impact Measurement Scale) *Indicates quality scores for RCTs as per the PEDro scale.