An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

Figures & data

Figure 1 Summary of patient flow throughout study.

Abbreviations: NeP, neuropathic pain; PN, polyneuropathy.

Table 1 Clinical features and baseline characteristics of patients and control subjects studied

Clinical features	Monotherapy		Adjuvant therapy
	Venlafaxine (n = 43)	Gabapentin (n = 52)	Venlafaxine (n = 45)	Gabapentin (n = 64)	Control group (no therapy) (n = 29)
Age (mean ± SD)	59 ± 7	61 ± 9	56 ± 5	61 ± 6	62 ± 9
Female sex (%)	27 (63%)	31 (60%)	28 (62%)	37 (58%)	17 (59%)
Age of onset of NeP symptoms (years), mean ± SD	57 ± 11	58 ± 13	55 ± 9	58 ± 15	59 ± 16
Age of initiation of NeP therapy initiation (years), mean ± SD	58 ± 10	59 ± 14	55 ± 9	60 ± 14	60 ± 15
Etiology of PN
Idiopathic	6	8	7	12	5
Diabetic	12	16	14	17	8
Vit B12	9	11	6	7	3
MGUS	4	2	2	5	3
Alcoholic	2	4	5	9	1
Immune	3	4	2	6	3
Hereditary	2	3	2	2	1
Other	5	4	7	6	5
TCSS	12.3 ± 4.3	12.0 ± 3.8	11.9 ± 4.2	13.2 ± 3.5	12.5 ± 4.0
Pre-existing NeP Therapies, number of patients using and average dose	N/A	N/A	Amitryptyline (n = 15), 17.5 ± 12.5 mg/d Nortriptyline (n = 2), 50 mg/d	Amitryptyline (n = 22), 18.3 ± 12.9 mg/d Nortriptyline (n = 2), 25 ± 0 mg/d	N/A
			Carbamazepine (n = 2), 300 ± 141 mg/d
			Valproic acid (n = 1) 750 mg/d	Carbamazepine (n = 5), 380 ± 148 mg/d
			Phenytoin (n = 2), 250 mg/d
			Nabilone (n = 3) 1.50 ± 0.50 mg/d Morphine (n = 14) 54 ± 27 mg/d Fentanyl (n = 1) 50 μg/d Oxycodone (n = 7) 33 ± 17 mg/d Acetaminophen (n = 4) 722 ± 368 mg/d Codeine (n = 2) 105 ± 86 mg/d	Phenytoin (n = 2), 250 ± 70 mg/d Venlafaxine (n = 3) 150 mg/d Morphine (n = 20) 48 ± 23 mg/d Fentanyl (n = 2) 63 ± 18 μg/d Oxycodone (n = 13 39 ± 18 mg/d Acetaminophen (n = 2) 650 ± 168 mg/d Codeine (n = 4) 141 ± 77 mg/d
Pre-existing side effects of NeP therapies
Sedation			14 (31%)	17 (26%)
Dizziness (lightheadedness)			10 (22%)	16 (25%)
Peripheral edema			1 (2%)	1 (2%)
Fatigue			14 (31%)	12 (19%)
Dry mouth			5 (11%)	5 (8%)
Headache			6 (13%)	4 (6%)
Other			15 (33%)	20 (31%)
Total responses of adverse effects			65	75
Number of patients with adverse effects prior to initiation of studied therapies			20 (44%)	25 (39%)
Duration of time using NeP therapy prior to initiation of studied therapies (months)			11.9 ± 5.2	14.6 ± 6.1

Notes: Data are presented as mean ± standard deviation, or as an absolute number. ANOVA tests were performed to compare groups receiving monotherapy as well as the two groups receiving adjuvant therapy.

* indicates a significant difference with ANOVA testing when the intervention group was compared to the control group.

Abbreviations: MGUS, monoclonal gammopathy of uncertain significance; NeP, neuropathic pain; PN, polyneuropathy; TCNS, Toronto Neuropathy Clinical Score.

Table 2 Parameters measured for monotherapy groups at baseline, 3 and 6 months after initiation of treatment

	Venlafaxine (n = 43)			Gabapentin (n = 52)
	Baseline	3 month	6 month	Baseline	3 month	6 month
Initiated/modified/achieved mean and actual doses at each time point	156.5 ± 42.7 mg/d 75 mg bid (n = 38) 150 mg bid (n = 3) 75 mg qhs (n = 2)	221.0 ± 54.3 mg/d	223.2 ± 57.3 mg/d	1684.6 ± 412.2 mg/d	2372.4 ± 561.4 mg/d	2295.5 ± 508.6 mg/d
		75 mg bid (n = 19)	75 mg bid (n = 16)	600 mg po tid (n = 34)	1200 mg po tid (n = 4)	1200 mg po tid (n = 2)
		150 mg bid (n = 17)	150 mg bid (n = 16)	600 mg po bid (n = 12)	900 mg po tid (n = 14)	900 mg po tid (n = 14)
		75 mg qhs (n = 1) 0 mg (n = 6)	75 mg qhs (n = 1) 0 mg (n = 10)	300/600/600 mg (n = 2)	600 mg po tid (n = 13)	600 mg po tid (n = 11)
				600/600/900 mg (n = 2)	600 mg po bid (n = 4)	600 mg po bid (n = 4)
				600/900/900 mg (n = 2)	600/600/900/900 mg (n = 2) 0 (n = 15)	600/600/900/900 mg (n = 2) 0 (n = 19)
VAS	46.0 ± 7.6	36.5 ± 7.8*	27.7 ± 9.5*,€	50.2 ± 13.5	41.5 ± 13.2*	33.8 ± 11.6*,€
Absolute and % Improvement in VAS since initiation		9.5 ± 4.9 (20.6%)¥	18.3 ± 6.8 (42.0%)¥		8.7 ± 5.1 (17.3%)¥	16.4 ± 9.1 (32.7%)¥
Side effects of NeP monotherapies
Sedation		12 (28%)	14 (33%)		28 (54%)	31 (60%)
Dizziness/lightheadedness		8 (19%)	11 (26%)		17 (33%)	20 (39%)
Peripheral edema		0 (0%)	1 (2%)		2 (4%)	4 (8%)
Fatigue		10 (23%)	12 (28%)		14 (27%)	16 (33%)
Dry mouth		5 (12%)	5 (12%)		8 (15%)	8 (15%)
Headache		1 (2%)	2 (5%)		3 (6%)	3 (6%)
Gastric upset		6 (14%)	6 (14%)		1 (2%)	1 (2%)
Sexual dysfunction		2 (5%)	3 (7%)		2 (4%)	2 (4%)
Other		14 (29%)	17 (35%)		5 (10%)	7 (13%)
Total responses of adverse effects		58	71		79	90
Number of patients with adverse effects		20 (47%)	22 (51%)		30 (47%)	31 (48%)
Reasons for discontinuing (accumulative)
Sedation		1 (2%)	1 (2%)		5 (10%)	5 (10%)
Dizziness/lightheadedness		1 (2%)	1 (2%)		6 (12%)	6 (12%)
Gastric upset		1 (2%)	1 (2%)		0 (0%)	0 (0%)
Inefficacy		3 (7%)	7 (16%)		4 (8%)	8 (15%)
EQ-5D Mobility Score	1.4 ± 0.6		1.4 ± 0.5	1.4 ± 0.7		1.4 ± 0.6
EQ-5D Self Care Score	1.6 ± 0.6		1.4 ± 0.5	1.4 ± 0.5		1.4 ± 0.5
EQ-5D Usual Activities Score	1.5 ± 0.7		1.5 ± 0.6	1.4 ± 0.6		1.5 ± 0.6
EQ-5D Pain/Discomfort Score	2.4 ± 0.9		2.2 ± 0.6	2.6 ± 0.8		2.4 ± 0.7
EQ-5D Anxiety/Depression Score	1.7 ± 0.7		1.6 ± 0.6	1.6 ± 0.7		1.5 ± 0.6
EQ-5D Index Score	0.58 ± 0.16		0.65 ± 0.17	0.56 ± 0.17		0.61 ± 0.20
EQ-5D VAS	63.0 ± 14.5		65.2 ± 14.2	63.3 ± 16.9		67.2 ± 16.4
MOSSS domains
Sleep Disturbance	38.6 ± 16.5¥		27.2 ± 14.7*	36.8 ± 17.5¥		29.3 ± 16.6*
Somnolence	35.7 ± 17.6		31.1 ± 16.6	35.7 ± 18.7		31.7 ± 19.3
Sleep Adequacy	44.3 ± 20.7		60.5 ± 21.5*	49.3 ± 22.8		59.5 ± 23.9*
Snoring	14.2 ± 14.8		14.1 ± 15.2	15.4 ± 16.3		15.0 ± 16.6
Awaken Short of Breath or with Headache	15.3 ± 12.1		14.4 ± 13.8	16.0 ± 15.6		12.0 ± 13.1
Quantity of Sleep (hours)	5.6 ± 2.2¥		6.5 ± 2.3*	6.0 ± 2.3¥		6.4 ± 2.1
Sleep Problems Index	35.7 ± 11.7		28.2 ± 10.5*	33.1 ± 11.5		25.2 ± 11.6
HADS (Total)	14.1 ± 10.3		9.7 ± 6.0*	11.7 ± 9.7		10.0 ± 7.2
HADS-A	8.7 ± 5.2		5.9 ± 5.1*	8.0 ± 5.1		5.4 ± 6.8*
HADS-D	5.4 ± 4.7		3.8 ± 3.8	3.7 ± 4.6		4.6 ± 3.5
SF-36 domains
Physical Functioning	31.6 ± 22.5		47.6 ± 22.1*	36.1 ± 24.0		46.5 ± 25.1*
Role Physical	25.5 ± 13.0¥		33.4 ± 12.6	22.2 ± 10.9¥		30.2 ± 12.3
Bodily Pain	24.3 ± 20.2¥		37.6 ± 13.5*	26.9 ± 21.2¥		37.5 ± 20.0*
General Health	42.2 ± 20.5		54.3 ± 19.6*	45.2 ± 21.4		51.3 ± 21.9
Vitality	24.3 ± 14.3¥		30.5 ± 18.6*	19.8 ± 15.1¥		30.1 ± 15.0*
Social Functioning	33.2 ± 24.3		37.8 ± 22.1	40.1 ± 24.4		45.2 ± 24.2
Role Emotional	24.7 ± 23.9		30.2 ± 26.1	26.2 ± 25.1		30.4 ± 25.3
Mental Health	48.6 ± 22.8		61.8 ± 21.5*	51.2 ± 22.0		58.0 ± 22.4
BPI – pain severity
Worst Pain	6.6 ± 2.9		6.1 ± 2.0	6.2 ± 3.0		6.2 ± 2.8
Average Pain	5.2 ± 2.5		4.1 ± 2.1*	5.1 ± 2.4		4.2 ± 2.0*
Least Pain	3.6 ± 2.2¥		2.9 ± 1.8	3.0 ± 2.0		2.6 ± 2.0
Pain Now	4.9 ± 2.1		4.2 ± 1.7*	5.1 ± 2.2		4.4 ± 1.6*
Mean Severity	5.1 ± 2.0		4.3 ± 2.0*	4.9 ± 2.1		4.4 ± 1.8*
BPI – pain related interference
General Activity	5.6 ± 2.3¥		4.3 ± 1.9*	5.8 ± 2.5¥		4.8 ± 2.3*
Walking Ability	5.3 ± 2.4		4.2 ± 1.9*	5.5 ± 2.2		4.8 ± 2.2*
Normal Work	5.3 ± 2.3		4.4 ± 1.8*	5.5 ± 2.2		4.8 ± 2.1*
Relations with Others	5.6 ± 2.1		4.4 ± 1.8*	5.6 ± 2.0		4.7 ± 2.0*
Sleep	5.8 ± 2.6¥		4.7 ± 1.7*	6.0 ± 2.4¥		5.1 ± 2.1*
Enjoyment of Life	5.2 ± 2.5		4.2 ± 1.9*	5.9 ± 2.3		5.1 ± 2.1*
Mean Interference	5.5 ± 2.4¥		4.4 ± 2.3*	5.6 ± 2.5¥		4.9 ± 2.2

Notes: Data are presented as mean ± standard deviation. ANOVA tests were performed to compare groups receiving monotherapy at the same time points.

* indicates a significant difference with ANOVA testing when the timepoint data are compared to baseline data.

€ indicates a significant difference when 6-month data are compared to 3-month data.

¥ indicates a significant difference when the intervention is compared to the control group at the identical timepoint (Table 4).

Abbreviations: BPI, Brief Pain Inventory; EQ-5D, EuroQol 5 Domains; HADS, Hospital Anxiety and Depression Scale; MOSSS, Medical Outcomes Sleep Study Scale; NeP, neuropathic pain; QHS, at bedtime daily; VAS, visual analogue scale.

Table 3 Parameters measured for adjuvant groups at baseline, 3 and 6 months after initiation of treatment

Test	Venlafaxine (n = 45)			Gabapentin (n = 64)
	Baseline	3 month	6 month	Baseline	3 month	6 month
Initiated/modified/achieved mean and actual doses at each time point	141.7 ± 23.9 mg/d	218.7 ± 57.8 mg/d	216.4 ± 62.4 mg/d	1577.3 ± 375.8 mg/d	1867.4 ± 582.3 mg/d	1891.1 ± 588.9 mg/d
	75 mg bid (n = 40)	75 mg bid (n = 17)	75 mg bid (n = 16)	600 mg po tid (n = 34)	1200 mg po tid (n = 2)	1200 mg po tid (n = 2)
	75 mg qhs (n = 5)	150 mg bid (n = 20)	150 mg bid (n = 17)	600 mg po bid (n = 15)	900 mg po tid (n = 13)	900 mg po tid (n = 14)
		75 mg qhs (n = 3)	75 mg qhs (n = 3)	300/600/600 mg (n = 5)	600 mg po tid (n = 25)	600 mg po tid (n = 20)
		0 mg (n = 5)	0 mg (n = 9)	600/600/900 mg (n = 5)	600 mg po bid (n = 6)	600 mg po bid (n = 5)
				600/900/900 mg (n = 3)	300 mg po bid (n = 5)	300 mg po bid (n = 5)
					600/600/900/900 mg (n = 1)	0 (n = 18)
					0 (n = 12)
VAS	52.4 ± 17.7	42.3 ± 16.5*	32.7 ± 21.2*,€	49.9 ± 30.0	41.3 ± 26.2*	33.0 ± 21.2*,€
% Improvement in VAS since initiation		9.9 ± 6.1 (18.8%)¥	19.7 ± 8.6 (37.6%)¥		8.6 ± 5.3 (17.2%)¥	16.9 ± 9.6 (33.9%)¥
Number of patients discontinuing PGB/GBP		Intolerant (n = 3)	Intolerant (n = 3)		Intolerant (n = 9)	Intolerant (n = 10)
		Ineffective (n = 2)	Ineffective (n = 6)		Ineffective (n = 3)	Ineffective (n = 8)
Side effects during adjuvant therapies
Sedation		20 (44%)	22 (49%)		22 (34%)	22 (34%)
Dizziness/lightheadedness		13 (29%)	15 (33%)		16 (25%)	19 (30%)
Peripheral edema		0 (0%)	0 (0%)		5 (8%)	7 (11%)
Fatigue		13 (29%)	15 (33%)		6 (9%)	11 (17%)
Dry mouth		3 (7%)	3 (7%)		7 (11%)	8 (13%)
Headache		2 (4%)	2 (4%)		1 (1%)	3 (5%)
Other		23 (51%)	26 (58%)		14 (22%)	17 (27%)
Total responses of adverse effects		74	83		71	87
Number of patients with adverse effects prior to initiation of studied therapies		24 (53%)	27 (60%)		30 (47%)	31 (48%)
Reasons for discontinuing adjuvant therapy
Sedation		2 (4%)	2 (4%)		7 (11%)	7 (11%)
Dizziness/lightheadedness		1 (2%)	1 (2%)		2 (3%)	3 (5%)
Inefficacy		2 (4%)	6 (13%)		3 (5%)	8 (13%)
EQ-5D Mobility Score	1.2 ± 0.6		1.3 ± 0.6	1.3 ± 0.6		1.4 ± 0.5
EQ-5D Self Care Score	1.5 ± 0.6		1.2 ± 0.5*	1.2 ± 0.6		1.3 ± 0.5
EQ-5D Usual Activities Score	1.6 ± 0.6		1.5 ± 0.6	1.4 ± 0.7		1.4 ± 0.6
EQ-5D Pain/Discomfort Score	2.4 ± 0.8		2.3 ± 0.7	2.5 ± 0.9		2.2 ± 0.6*
EQ-5D Anxiety Score	1.6 ± 0.8		1.6 ± 0.6	1.6 ± 0.7		1.5 ± 0.6
EQ-5D Index Score	0.58 ± 0.20		0.61 ± 0.19	0.55 ± 0.24		0.57 ± 0.26
EQ-5D VAS	64.8 ± 16.9		66.9 ± 24.1	58.2 ± 26.9		64.5 ± 22.8
MOSSS Domains
Sleep disturbance	42.3 ± 15.8¥		30.1 ± 15.2*	40.4 ± 18.8¥		34.5 ± 17.1*
Somnolence	38.2 ± 16.4		32.6 ± 14.5	36.8 ± 16.9		34.7 ± 15.5
Sleep adequacy	42.6 ± 20.5		57.5 ± 8.5*	43.1 ± 18.4		45.5 ± 17.9
Snoring	13.3 ± 12.1		12.9 ± 13.2	15.1 ± 14.0		15.2 ± 14.2
Awaken short of breath or with headache	14.8 ± 11.4		15.1 ± 13.5	14.6 ± 13.8		14.5 ± 13.9
Quantity of sleep (hours)	5.5 ± 2.0¥		6.4 ± 2.1*	5.9 ± 1.8¥		6.4 ± 1.9
Sleep Problems Index	36.2 ± 12.0		27.3 ± 9.8*	36.7 ± 12.8		30.8 ± 12.6
HADS	15.8 ± 9.8		10.1 ± 7.2*	16.9 ± 12.6		14.1 ± 8.7
HADS-A	9.6 ± 6.0		5.5 ± 4.7*	11.5 ± 5.5		7.1 ± 7.8*
HADS-D	6.2 ± 4.9		4.6 ± 3.6	5.7 ± 5.9		7.0 ± 5.2
SF-36 Domains
Physical functioning	32.8 ± 21.6		43.8 ± 20.8*	35.4 ± 25.4		42.6 ± 23.4*
Role Physical	27.6 ± 14.2¥		35.2 ± 13.4	26.3 ± 9.9¥		29.4 ± 12.0
Bodily Pain	22.8 ± 19.6¥		38.7 ± 14.2*	26.2 ± 22.0¥		38.3 ± 19.1*
General Health	41.8 ± 19.7		49.6 ± 17.6	44.6 ± 20.2		47.4 ± 19.1
Vitality	22.8 ± 16.2¥		28.7 ± 17.7	21.3 ± 14.1		28.1 ± 14.2
Social Functioning	31.6 ± 21.5		34.6 ± 20.4	38.6 ± 25.4		43.1 ± 20.8
Role Emotional	25.5 ± 24.8		32.0 ± 25.1	25.8 ± 24.2		31.1 ± 23.5
Mental Health	44.4 ± 21.2		58.7 ± 20.2*	52.2 ± 20.7		59.1 ± 22.3
BPI – pain severity
Worst Pain	6.2 ± 3.0		6.0 ± 2.1	6.3 ± 2.9		6.1 ± 2.8
Average Pain	5.6 ± 2.4		4.6 ± 1.8*	5.7 ± 2.5		4.2 ± 1.8*
Least Pain	3.8 ± 1.9		3.2 ± 1.7	3.3 ± 2.0		2.8 ± 1.9
Pain Now	5.4 ± 2.2		4.0 ± 1.7	5.8 ± 2.5		4.3 ± 1.9
Mean Severity	5.3 ± 2.0		4.4 ± 2.1*	5.3 ± 2.4		4.4 ± 1.9*
BPI – pain related interference
General Activity	5.8 ± 2.3¥		5.1 ± 1.9	6.1 ± 2.6¥		5.1 ± 2.3*
Mood	6.1 ± 2.2		4.8 ± 1.8*	5.9 ± 2.6		5.0 ± 2.3*
Walking Ability	5.9 ± 2.5		4.8 ± 2.1*	5.7 ± 2.6		5.0 ± 2.2
Normal Work	5.6 ± 2.4		4.8 ± 2.0	6.1 ± 2.5		5.0 ± 2.1*
Relations with Others	5.6 ± 2.3		4.9 ± 1.7*	5.0 ± 2.0		4.9 ± 2.0
Sleep	6.2 ± 2.4¥		4.5 ± 1.8*	6.4 ± 2.5¥		5.2 ± 2.2*
Enjoyment of Life	5.8 ± 2.4		4.9 ± 2.2	6.0 ± 2.4		5.0 ± 2.2*
Mean Interference	5.8 ± 2.5¥		4.8 ± 2.3*	5.8 ± 2.6¥		5.0 ± 2.4*

Notes: Data are presented as mean ± standard deviation. ANOVA tests were performed to compare groups receiving adjuvant therapy at the same time points.

* indicates a significant difference with ANOVA testing when the timepoint data are compared to baseline data.

€ indicates a significant difference when 6-month data are compared to 3-month data.

¥ indicates a significant difference when the intervention is compared to the control group at the identical timepoint (Table 4).

Abbreviations: BPI, Brief Pain Inventory; EQ-5D, EuroQol 5 Domains; GBP, gabapentin; HADS, Hospital Anxiety and Depression Scale; MOSSS, Medical Outcomes Sleep Study Scale; NeP, neuropathic pain; PGB, ; VAS, visual analogue scale.

Table 4 Parameters measured for the control groups at baseline, 3 and 6 months after initiation of treatment

	Control group (n = 29)
	Baseline	3 month	6 month
VAS	29.6 ± 12.1	30.3 ± 12.7	30.4 ± 1.5
Absolute and % Improvement in VAS since initiation		−0.7 ± 6.8 (−2.3%)	−0.8 ± 7.2 (−2.7%)
EQ-5D Mobility Score	1.3 ± 0.8		1.3 ± 0.8
EQ-5D Self Care Score	1.2 ± 0.8		1.3 ± 0.7
EQ-5D Usual Activities Score	1.3 ± 1.0		1.3 ± 0.9
EQ-5D Pain/Discomfort Score	2.1 ± 0.9		2.1 ± 0.9
EQ-5D Anxiety/Depression Score	1.6 ± 0.9		1.6 ± 0.8
EQ-5D Index Score	0.68 ± 0.26		0.67 ± 0.28
EQ-5D VAS	69.8 ± 21.5		69.3 ± 21.2
MOSSS Domains
Sleep Disturbance	28.4 ± 21.2		28.8 ± 22.0
Somnolence	27.3 ± 21.5		28.4 ± 22.5
Sleep Adequacy	56.4 ± 27.2		55.8 ± 26.8
Snoring	13.7 ± 16.6		14.0 ± 14.6
Awaken Short of Breath or with Headache	12.4 ± 17.1		14.3 ± 19.2
Quantity of Sleep (hours)	7.2 ± 2.8		7.1 ± 2.9
Sleep Problems Index	23.6 ± 16.7		24.1 ± 18.2
HADS (total)	9.4 ± 10.2		9.2 ± 10.8
HADS-A	5.3 ± 11.6		5.1 ± 11.8
HADS-D	4.1 ± 11.9		4.1 ± 11.6
SF-36 Domains
Physical Functioning	48.9 ± 31.3		49.7 ± 32.0
Role Physical	36.5 ± 17.8		35.1 ± 16.5
Bodily Pain	40.2 ± 19.2		42.6 ± 15.2
General Health	59.7 ± 24.7		54.4 ± 23.8
Vitality	37.4 ± 23.5		39.0 ± 24.1
Social Functioning	51.2 ± 28.3		54.7 ± 26.2
Role Emotional	40.6 ± 29.9		41.1 ± 28.0
Mental Health	63.7 ± 27.1		62.5 ± 24.6
BPI – pain severity
Worst Pain	5.4 ± 3.5		5.7 ± 3.4
Average Pain	4.1 ± 3.3		4.2 ± 3.2
Least Pain	1.5 ± 2.9		1.6 ± 3.1
Pain Now	4.7 ± 3.2		4.5 ± 3.0
Mean Severity	3.9 ± 3.1		4.0 ± 3.2
BPI – pain related interference
General Activity	4.1 ± 3.1		4.0 ± 3.1
Mood	3.2 ± 3.2		3.4 ± 3.1
Walking Ability	3.5 ± 3.0		3.7 ± 2.8
Normal Work	3.0 ± 3.1		3.0 ± 3.0
Relations with Others	3.2 ± 2.7		3.0 ± 2.8
Sleep	2.6 ± 3.1		2.5 ± 3.0
Enjoyment of Life	4.1 ± 2.8		3.9 ± 2.7
Mean Interference	3.4 ± 3.0		3.4 ± 3.1

Notes: Data are presented as mean ± standard deviation. ANOVA tests were performed to compare groups receiving monotherapy at the same time points.

Abbreviations: BPI, Brief Pain Inventory; EQ-5D, EuroQol 5 Domains; HADS, Hospital Anxiety and Depression Scale; MOSSS, Medical Outcomes Sleep Study Scale; NeP, neuropathic pain; VAS, visual analogue scale.

Figure 2 Patient global impression of change (PGIC) was analyzed using a Cochran-Mantel-Haenszel procedure, adjusting for center in each case. Patients reported a significant perceived benefit with monotherapy compared to control group patients for each of venlafaxine (A) and gabapentin (B), as well as with adjuvant therapy for each of venlafaxine (C) and gabapentin (D). In contrast, the control group receiving no therapy had no significant change in PGIC reported (E).