Clinical characteristics, pharmacotherapy, and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants

Figures & data

Table 1.  Diagnostic codes used to identify relevant comorbidities.

Comorbidities	ICD-9-CM codes
Cardiovascular disorders
Myocardial infarction	410.X, 412.X
Congestive heart failure	398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 425.4–425.9, 428.X
Peripheral vascular disease	093.0, 437.3, 440.X, 441.X, 443.1–443.9, 447.1, 557.1, 557.9, V43.4
Cerebrovascular disease	362.34, 430.X–438.X
Coronary heart disease	410.XX–414.XX
Hypertension	401.X
Hyperlipidemia	272.0, 272.1, 272.2, 272.4
Gastrointestinal disorders
Irritable bowel syndrome	564.1
Gastroesophageal reflux disease	530.11, 530.81
Gastritis	535.00–535.5X
Duodenitis	535.6X
Other	520.5–530.10, 530.19–530.7, 530.82–530.9, 536.0–537.X, 540.0–543.X, 550.00–553.XX, 555.0–558.X, 560.XX, 562.00–562.01, 562.10–562.11, 564.2–569.2, 569.41–569.81, 569.84–577.9, 579.X
Mental disorders
Depression	296.2X, 296.3X, 300.4, 311
Bipolar disorder	296.4X, 296.5X, 296.6X, 296.7
Anxiety	300.00, 300.5, 300.09, 300.20, 300.22, 300.23, 300.29, 300.3, 308.3
Generalized anxiety disorder	300.02
Panic disorder	300.01, 300.21
Post-traumatic stress disorder	309.81
Sleep disorders
Insomnia/sleep disorders	780.5X, 307.4X, 347.0X, 347.1X, V69.4
Sleep apnea	780.51, 780.53, 780.57
Musculoskeletal pain conditions
Lupus	710
Diffuse diseases of connective tissue	710.1, 710.2, 710.3, 710.4, 710.5, 710.8, 710.9
Arthritis and other arthropathies	711.XX, 712.XX, 713.X, 714.4X, 714.8X. 714.9X, 716.XX, 717.XX, 718.XX, 719.XX
Rheumatoid arthritis	714.0, 714.1, 714.2
Low back pain	720.0, 720.1, 720.2, 721.3, 722.10, 722.32, 722.5, 722.83, 722.93, 724.00, 724.02, 724.2, 724.5, 724.6, 724.70, 724.71, 724.79, 738.4, 739.3, 739.4, 756.11, 756.12, 805.4, 805.6, 846.0, 846.1, 846.2, 846.3, 846.8, 846.9, 847.2, 847.3, 847.4
Back and neck pain, other than low back pain	720.81, 720.89, 720.9, 721.0, 721.2, 721.5, 721.6, 721.7, 721.8, 721.90, 722.11, 722.30, 722.31, 722.39, 722.4, 722.6, 722.80, 722.81, 722.82, 722.90, 722.91, 722.92, 723.X (except 723.4), 724.01, 724.1, 724.8, 724.9, 737.10, 737.11, 737.12, 737.19, 737.20, 737.21, 737.22, 737.29, 737.30, 756.10, 756.13, 756.14, 756.15, 756.16, 756.17, 756.19, 805.8, 847.9
Rheumatism, excluding the back	725–728.9, 729.3–729.9
Other	730.00–739.X
Neuropathic pain conditions
Postherpetic neuralgia	53.1
Carpal tunnel syndrome	354
Causalgias	337.2X, 354.4, 355.71, 355.9
Neuritis radiculitis unspecified	729.2
Trigeminal neuralgia	350.1
Atypical facial pain	350.2
Phantom limb pain	353.6
Autonomic neuropathies	337.1, 337.9
Other polyneuropathies	344.6, 353.0, 353.1, 353.8, 353.9, 354.1, 354.2, 354.3, 354.5, 354.8, 354.9, 355.0, 355.1, 355.2, 355.3, 355.4, 355.5, 355.6, 355.79, 355.8, 357.1, 357.3, 357.4, 357.5, 357.6, 357.7, 357.8, 357.9
Back and neck pain with neuropathic involvement	721.1, 721.41, 721.42, 721.91, 722.7X, 723.4, 724.3, 724.4
Symptoms, signs, and ill-defined conditions
Obesity	278.00, 278.01, 278.02
Headache NOS	784.0X
Chest pain	786.5X
Abdominal pain	789.0X
Anxiety-related symptoms	780.4, 785.0, 785.1, 786.01, 786.05, 786.09
Gastric-related symptoms	787.0, 787.01–787.03, 787.1–787.3, 787.9, 787.91, 787.99
Other	780.02–780.39, 780.6, 780.8–783.9, 784.1–784.9, 785.2–786.00, 786.02–786.04, 786.06, 786.07, 786.1–786.4, 786.6–786.9, 787.4–787.7, 788.0–788.9, 789.1–796.9, 799.X

ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; NOS, not otherwise specified.

Table 2.  Demographic and clinical characteristics of the study cohorts.

Demographic/clinical characteristic*	Pregabalin (n = 898)	TCAs (n = 898)	p^a
Age, y
Mean (SD)	47.9 (9.6)	48.5 (9.9)	0.1959
Median	49	49
Age group, n (%)
18–34 y	89 (9.9)	83 (9.2)	0.0513
35–44 y	211 (23.5)	209 (23.3)
45–54 y	368 (41.0)	333 (37.1)
55–64 y	218 (24.3)	246 (27.4)
≥ 65 y	12 (1.3)	27 (3.0)
Gender, n (%)
Female	787 (87.6)	760 (84.6)	0.0652
Male	111 (12.4)	138 (15.4)
Mean Charlson Comorbidity Index score (SD)	2.10 (1.63)	2.08 (1.60)	0.8707
Cardiovascular disorders, n (%)
Myocardial infarction	7 (0.8)	7 (0.8)	1.0000
Congestive heart failure	14 (1.6)	12 (1.3)	0.6928
Peripheral vascular disease	27 (3.0)	29 (3.2)	0.7860
Cerebrovascular disease	27 (3.0)	43 (4.8)	0.0511
Coronary heart disease	50 (5.6)	66 (7.3)	0.1245
Hypertension	311 (34.6)	281 (31.3)	0.1321
Hyperlipidemia	321 (35.8)	337 (37.5)	0.4333
Gastrointestinal disorders, n (%)
Irritable bowel syndrome	74 (8.2)	69 (7.7)	0.6630
Gastroesophageal reflux disease	197 (21.9)	216 (24.0)	0.2867
Gastritis	83 (9.2)	81 (9.0)	0.8699
Duodenitis	3 (0.3)	3 (0.3)	1.0000
Other	247 (27.5)	299 (33.3)	0.0076
Mental disorders, n (%)
Depression	300 (33.4)	257 (28.6)	0.0283
Bipolar disorder	14 (1.6)	19 (2.1)	0.3797
Anxiety	122 (13.6)	132 (14.7)	0.4983
Generalized anxiety disorder	34 (3.8)	47 (5.2)	0.1394
Panic disorder	28 (3.1)	27 (3.0)	0.8911
Post-traumatic stress disorder	9 (1.0)	12 (1.3)	0.5102
Sleep disorders, n (%)
Insomnia/sleep disorders	209 (23.3)	220 (24.5)	0.5427
Sleep apnea	87 (9.7)	59 (6.6)	0.0156
Musculoskeletal pain conditions, n (%)
Lupus	21 (2.3)	17 (1.9)	0.5119
Diffuse diseases of connective tissue	24 (2.7)	15 (1.7)	0.1451
Arthritis and other arthropathies	494 (55.0)	447 (49.8)	0.0264
Rheumatoid arthritis	62 (6.9)	31 (3.4)	0.0010
Low back pain	499 (55.6)	565 (62.9)	0.0015
Back and neck pain, other than low back pain	420 (46.8)	471 (52.4)	0.0161
Rheumatism, excluding the back	494 (55.0)	474 (52.8)	0.3438
Other	293 (32.6)	366 (40.8)	0.0004
Neuropathic pain conditions, n (%)
Diabetic neuropathy	5 (0.6)	7 (0.8)	0.5624
Postherpetic neuralgia	4 (0.4)	1 (0.1)	0.1791
Carpal tunnel syndrome	61 (6.8)	58 (6.5)	0.7760
Causalgia	34 (3.8)	30 (3.3)	0.6106
Neuritis/Radiculitis	48 (5.3)	54 (6.0)	0.5407
Trigeminal neuralgia	4 (0.4)	8 (0.9)	0.2466
Atypical facial pain	3 (0.3)	4 (0.4)	0.7049
Phantom limb pain	0	0	–
Autonomic neuropathies	3 (0.3)	2 (0.2)	0.6543
Other polyneuropathies	67 (7.5)	66 (7.3)	0.9282
Back and neck pain with neuropathic involvement	265 (29.5)	257 (28.6)	0.6776
Symptoms, signs, and ill-defined conditions, n (%)
Obesity	67 (7.5)	62 (6.9)	0.6477
Headache NOS	203 (22.6)	282 (31.4)	<0.0001
Chest pain	189 (21.0)	209 (23.3)	0.2558
Abdominal pain	226 (25.2)	267 (29.7)	0.0302
Anxiety-related symptoms	229 (25.5)	232 (25.8)	0.8713
Gastric-related symptoms	201 (22.4)	230 (25.6)	0.1091
Other	588 (65.5)	580 (64.6)	0.6922

*Clinical characteristics defined as one or more claim(s) for each comorbid condition in the pre-index period.

^aChi-square or Fisher exact tests and analysis of variance models were used to calculate the statistical significance of differences between pregabalin and TCAs for proportions and means, respectively.

TCAs, tricyclic antidepressants; SD, standard deviation; NOS, not otherwise specified.

Table 3.  Number of patients prescribed pregabalin and TCAs who had ≥ 1 claims for pain-related medications in the pre-index and follow-up periods.

Medications	Patients prescribed pregabalin, n (%) (n = 898)			Patients prescribed TCAs, n (%) (n = 898)
	Pre-index	Follow-up	p*	Pre-index	Follow-up	p*
Long-acting opioids	183 (20.4)	192 (21.4)	0.2786	113 (12.6)	107 (12.0)	0.4142
Short-acting opioids	263 (29.3)	288 (32.1)	0.0602	209 (23.3)	207 (23.0)	0.8808
Strong opioids	330 (36.7)	353 (39.3)	0.0699	249 (27.7)	242 (27.0)	0.5967
Weak opioids	497 (55.3)	491 (54.7)	0.6924	433 (48.2)	433 (48.2)	<0.0001
Any opioids	636 (70.8)	643 (71.6)	0.5924	521 (58.0)	523 (58.2)	0.8937
COX-2 inhibitors	69 (7.7)	93 (10.4)	0.0088	52 (5.8)	71 (7.9)	0.0167
Non-selective NSAIDs	389 (43.3)	357 (39.8)	0.0405	331 (36.9)	340 (37.9)	0.5760
Any NSAIDs	429 (47.8)	416 (46.3)	0.4100	364 (40.5)	383 (42.6)	0.2359
SSRIs	296 (33.0)	281 (31.3)	0.1900	261 (29.1)	259 (28.8)	0.8720
SNRIs	337 (37.5)	334 (37.2)	0.8206	170 (18.9)	175 (19.5)	0.6547
TCAs	43 (4.8)	71 (7.9)	0.0047	206 (22.9)	898 (100.0)	<0.0001
Anticonvulsants^a	257 (28.6)	209 (23.3)	0.0009	225 (25.1)	303 (33.7)	<0.0001
Muscle relaxants	463 (51.6)	445 (49.5)	0.2270	377 (42.0)	345 (38.4)	0.0381
Benzodiazepines	372 (41.4)	379 (42.2)	0.5924	300 (33.4)	305 (34.0)	0.7117
Sedative/Hypnotics	304 (33.8)	297 (33.1)	0.5345	246 (27.4)	215 (23.9)	0.0164
Tramadol	249 (27.7)	226 (25.2)	0.0821	191 (21.3)	172 (19.1)	0.1319
Salicylates	14 (1.6)	12 (1.3)	0.5637	26 (2.9)	21 (2.3)	0.3173
Miscellaneous agents	94 (10.5)	85 (9.5)	0.3346	113 (12.6)	104 (11.6)	0.3798
Tetracyclic and miscellaneous antidepressants	256 (28.5)	232 (25.8)	0.0285	164 (18.3)	157 (17.5)	0.5211
Topical agents approved for neuropathic pain	97 (10.8)	136 (15.1)	0.0008	59 (6.6)	74 (8.2)	0.0874
Topical corticosteroids	117 (13.0)	119 (13.2)	0.8575	105 (11.7)	112 (12.5)	0.5377
ADHD drugs	54 (6.0)	68 (7.6)	0.0433	36 (4.0)	46 (5.1)	0.0863
Triptans	95 (10.6)	93 (10.4)	0.7728	105 (11.7)	113 (12.6)	0.2935
DMARDs	91 (10.1)	87 (9.7)	0.5716	67 (7.5)	71 (7.9)	0.5791
IA injections	153 (17.0)	167 (18.6)	0.2967	134 (14.9)	110 (12.2)	0.0455
Corticosteroids	278 (31.0)	269 (30.0)	0.5927	241 (26.8)	248 (27.6)	0.6648

*McNemar test for difference between pre- and post-index values.

^aExcludes pregabalin for the pregabalin cohort.

TCAs, tricyclic antidepressants; COX-2, cyclooxygenase 2; NSAIDs, non-steroidal anti-inflammatory drugs; SSRIs, selective serotonin reuptake inhibitors; SNRIs, serotonin-norepinephrine reuptake inhibitors; ADHD, attention-deficit/hyperactivity disorder; DMARDs, disease-modifying anti-rheumatic drugs; IA, intra-articular.

Table 4.  Medication use (among users) for pain-related medications in the pre-index and follow-up periods.

Medications	Number of prescriptions
	Patients prescribed pregabalin (n = 898)					Patients prescribed TCAs (n = 898)
	Pre-index		Follow-up		p*	Pre-index		Follow-up		p*
	Mean	Median (IQR)	Mean	Median (IQR)		Mean	Median (IQR)	Mean	Median (IQR)
Long-acting opioids	10.6	11 (6.0–13.0)	10.6	11 (5.0–13.0)	0.1344	8.9	8 (2.0–12.0)	9.2	9 (2.0–13.0)	0.6601
Short-acting opioids	8.1	6 (2.0–12.0)	8.1	6 (2.0–12.0)	0.1754	6.7	4 (1.0–10.0)	7.0	4 (2.0–11.0)	0.1831
Strong opioids	11.0	8 (3.0–16.0)	11.3	9 (2.0–15.0)	0.0002	7.9	3 (1.0–12.0)	8.1	3.5 (1.0–12.0)	0.6023
Weak opioids	6.5	4 (2.0–10.0)	6.3	4 (2.0–10.0)	0.1910	5.8	3 (1.0–8.0)	6.0	3 (1.0–8.0)	0.3644
Any opioids	10.8	8 (3.0–15.0)	11.0	8 (3.0–15.0)	0.0376	8.6	4 (2.0–12.0)	8.7	5 (2.0–13.0)	0.4453
COX-2 inhibitors	3.8	3 (1.0–5.0)	3.8	2 (1.0–5.0)	0.0584	3.5	2.5 (1.0–5.0)	3.6	2 (1.0–5.0)	0.0071
Nonselective NSAIDs	3.7	3 (1.0–5.0)	3.8	3 (1.0–5.0)	0.1103	3.1	2 (1.0–4.0)	3.4	2 (1.0–4.0)	0.0629
Any NSAIDs	4.0	3 (1.0–5.0)	4.1	3 (1.0–5.5)	0.7174	3.3	2 (1.0–4.0)	3.7	2 (1.0–5.0)	0.0043
SSRIs	6.1	5 (3.0–9.0)	5.9	5 (3.0–9.0)	0.2021	5.3	4 (2.0–8.0)	5.7	5 (2.0–9.0)	0.4255
SNRIs	6.6	5 (3.0–10.0)	6.8	6 (3.0–10.0)	0.6673	6.0	5 (2.0–9.0)	5.9	5 (3.0–9.0)	0.8359
TCAs	2.0	1 (1.0–3.0)	2.5	2 (1.0–3.0)	0.0047	2.1	2 (1.0–3.0)	3.8	2 (1.0–5.0)	<0.0001
Anticonvulsants^a	5.8	4 (2.0–8.0)	5.7	4 (2.0–8.0)	0.0012	4.8	3 (1.0–7.0)	4.9	3 (1.0–7.0)	<0.0001
Muscle relaxants	5.6	4 (1.0–8.0)	5.7	4 (2.0–8.0)	0.1493	4.4	3 (1.0–6.0)	4.5	3 (1.0–6.0)	0.4643
Benzodiazepines	6.5	5 (2.0–10.5)	6.6	6 (2.0–10.0)	0.3407	5.6	4 (2.0–8.0)	6.0	4 (2.0–9.0)	0.1599
Sedative/Hypnotics	6.5	5 (2.0–10.5)	6.8	6 (2.0–11.0)	0.9587	5.5	3 (1.0–9.0)	6.2	5 (2.0–10.0)	0.9975
Tramadol	4.8	3 (1.0–7.0)	5.3	3 (1.0–7.0)	0.6991	4.0	2 (1.0–6.0)	4.8	3 (1.0–7.0)	0.9285
Salicylates	3.1	2 (1.0–3.0)	2.9	2 (1.0–4.5)	0.6174	4.1	2 (1.0–5.0)	5.2	3 (1.0–9.0)	0.5646
Miscellaneous agents	2.9	2 (1.0–3.0)	3.1	1 (1.0–3.0)	0.4091	3.6	2 (1.0–4.0)	3.7	2 (1.0–3.0)	0.5481
Tetracyclic and miscellaneous antidepressants	6.1	5 (2.0–10.0)	6.3	5 (2.0–10.0)	0.0523	5.4	3 (2.0–8.0)	5.1	3 (1.0–7.0)	0.2153
Topical agents approved for neuropathic pain	2.5	1 (1.0–4.0)	2.2	2 (1.0–3.0)	0.0267	2.2	1 (1.0–3.0)	2.3	1 (1.0–3.0)	0.1561
Topical corticosteroids	2.0	1 (1.0–2.0)	2.3	1 (1.0–2.0)	0.4434	1.7	1 (1.0–2.0)	1.9	1 (1.0–2.0)	0.2564
ADHD drugs	6.4	5.5 (2.0–9.0)	5.6	3 (1.0–9.0)	0.2761	5.8	4 (1.0–9.0)	5.5	5 (2.0–8.0)	0.0702
Triptans	5.6	4 (2.0–8.0)	5.1	4 (1.0–8.0)	0.5672	5.3	4 (2.0–7.0)	5.1	3 (2.0–7.0)	0.2588
Corticosteroids	2.2	1 (1.0–2.0)	2.1	1 (1.0–3.0)	0.4934	2.2	1 (1.0–2.0)	2.0	1 (1.0–2.0)	0.5098

*Wilcoxon signed rank tests for difference between pre- and post-index values.

^aExcludes pregabalin for the pregabalin cohort.

TCAs, tricyclic antidepressants; IQR, interquartile range; COX-2, cyclooxygenase 2; NSAIDs, non-steroidal anti-inflammatory drugs; SSRIs, selective serotonin reuptake inhibitors; SNRIs, serotonin-norepinephrine reuptake inhibitors; ADHD, attention-deficit/hyperactivity disorder.

Table 5.  Healthcare resource use among patients prescribed pregabalin and TCAs in the pre-index and follow-up periods.

Resource use categories	Healthcare resource use, d
	Patients prescribed pregabalin (n = 898)							Patients prescribed TCAs (n = 898)
	Pre-index			Follow-up			p*	Pre-index			Follow-up			p*
	n (%)	Mean	Median (IQR)	n (%)	Mean	Median (IQR)		n (%)	Mean	Median (IQR)	n (%)	Mean	Median (IQR)
Outpatient visits
Physician office visits	896 (99.8)	20.0	16 (9.0–26.0)	893 (99.4)	19.7	15 (10.0–25.0)	0.2723	897 (99.9)	22.0	18 (10.0–29.0)	890 (99.1)	20.5	16 (10.0–26.0)	0.0006
ED visits	257 (28.6)	2.2	1 (1.0–2.0)	283 (31.5)	1.9	1 (1.0–2.0)	0.5496	285 (31.7)	2.2	1 (1.0–2.0)	268 (29.8)	2.1	1 (1.0–2.0)	0.2451
Other outpatient visits	893 (99.4)	12.8	10 (6.0–17.0)	879 (97.9)	13.0	10 (6.0–17.0)	0.1248	888 (98.9)	13.5	10 (6.0–17.0)	876 (97.5)	13.4	10 (6.0–17.0)	0.0612
Total outpatient visits	896 (100)	27.0	22 (13.0–35.0)	896 (100)	26.6	21 (13.0–35.0)	0.2994	898 (100)	29.7	25 (15.0–39.0)	895 (100)	27.8	22 (13.0–36.0)	0.0004
Hospitalizations	111 (12.4)	8.4	4 (3.0–8.0)	118 (13.1)	8.2	4 (3.0–9.0)	0.4583	131 (14.6)	6.8	3 (2.0–7.0)	90 (10.0)	7.9	5 (3.0–8.0)	0.0545

*Wilcoxon signed rank tests for difference between pre- and post-index values.

TCAs, tricyclic antidepressants; IQR, interquartile range; ED, emergency department.

Table 6.  Direct healthcare costs among patients prescribed pregabalin and TCAs in the pre-index and follow-up periods.

Cost category	Healthcare costs, $
	Patients prescribed pregabalin (n = 826)					Patients prescribed TCAs (n = 826)
	Pre-index		Follow-up		p*	Pre-index		Follow-up		p*
	Mean	Median (IQR)	Mean	Median (IQR)		Mean	Median (IQR)	Mean	Median (IQR)
Total medication costs	5,203.9	3,258.4	6,366.7	4,422.0	<0.0001	3,912.9	2,054.6	4,280.6	2,395.3	<0.0001
		(1,480.9–6,698.2)		(2,050.5–7,523.3)			(867.9–4,427.4)		(950.9–5,043.2)
Outpatient visits
Physician office visits	1,675.1	1,208.1	1,737.9	1,189.5	0.7857	1,944.9	1,376.9	1,852.0	1,311.2	0.2094
		(757.4–2,042.0)		(747.3–2,113.6)			(831.0–2,412.8)		(753.6–2,290.9)
ED visits	405.8	0	403.0	0	0.3660	457.6	0	428.2	0	0.6164
		(0.0–241.0)		(0.0–323.3)			(0.0–319.1)		(0.0–237.8)
Other outpatient visits	5,181.8	2,646.3	5,601.6	2,697.9	0.8110	5,793.9	2,922.9	6,090.5	2,690.5	0.1160
		(919.5–6,362.1)		(862.8–6,020.23)			(1,088.6–6,568.1)		(799.8–6,489.0)
Total outpatient visits	7,262.7	4,784.2	7,742.5	4,511.4	0.7873	8,196.3	5,228.0	8,370.7	4,652.5	0.1724
		(2,145.0–8,990.9)		(2,126.1–8,610.6)			(2,564.7–9,820.2)		(2,157.2–9,537.6)
Hospitalizations	3,450.0	0	3,233.9	0	0.8821	2,730.5	0	1,956.5	0	0.0501
		(0.0–0.0)		(0.0–0.0)			(0.0–0.0)		(0.0–0.0)
Total costs	15,916.6	9,934.7	17,343.1	10,689.1	<0.0001	14,839.8	8,771.2	14,607.8	8,379.3	0.3635
		(5,386.7–17,531.1)		(6,131.3–18,491.2)			(4,379.7–16,679.0)		(4,291.0–16,433.6)

*Wilcoxon signed rank tests for difference between pre- and post-index values.

TCAs, tricyclic antidepressants; IQR, interquartile range; ED, emergency department.