Nonsteroidal anti-inflammatory drugs in the treatment of low back pain

Figures & data

Table 1 Classification of nonsteroidal anti-inflammatory drugs

Compounds	Products
Salicylates	Aspirin, diflusinal, salsalate
Propionic acid derivatives	Ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, loxoprofen
Enolic acid (oxicam) derivatives	Piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam, phenylbutazone
Fenamic acid derivatives	Mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid
Alkanones	Nabumetone
Acetic acid derivatives	Indomethacin, sulindac, etodolac, ketorolac, diclofenac, nabumetone
Diaryl heterocyclic compounds	Celecoxib, valdecoxib, rofecoxib, etoricoxib
Sulphonanilides	Nimesulide
Others	Licofelone

Table 2 Common nonsteroidal anti-inflammatory drugs

NSAIDs	Typical adult dose (oral unless otherwise notated)	T1/2	Cox-1	Cox-2 selectivity	Comments
Aspirin	40–80 mg/day*	2–3 hours	Permanent platelet
	325–650 mg 4–6 hourly**		Cox-1 inhibition
	1 g 4–6 hourly***		+
Acetaminophen	10–15 mg/kg every 4–6 hours	2 hours	Weak nonspecific inhibitor
Indomethacin	25 mg 2–3 times/day; 75–100 mg at night	2.5 hours	++		10–40× more potent than ASA side effects: headache, neutropenia, thrombocytopenia
Ketorolac	30 mg IV or 60 mg IV	4–6 hours	++++		Potent analgesic
					Poor anti-inflammatory
Diclofenac	50 mg 3 times/day or 75 mg twice/day	1–2 hours	++	<5-fold COX 2	Highly potent
Mefenamic acid	500 mg load, then 250 mg every 6 hours	3–4 hours	++		Similar efficacy as ASA Central action
Ibuprofen	200–800 mg every 4–6 hours	2–4 hours	++		Similar efficacy as ASA
Naproxen	250 mg 4 times/day or 500 mg twice/day	14 hours	++		More potent than ASA
Fenoprofen	200 mg 4–6 times/day; 300–600 mg 3–4 times/day	2 hours	+
Ketoprofen	50–75 mg 3–4 times/day	2 hours	+++
Piroxicam	20 mg/day	45–50 hours	++	<5-fold Cox-2	Similar efficacy as ASA, better tolerated
Meloxicam	7.5–15 mg/day	15–20 hours	++	Cox-2 selectivity
Celecoxib	100 mg 1–2 times/day	6–12 hours		Highly selective

Notes:

* antiplatelet;

** pain/fever;

*** rheumatic fever.

Abbreviations: ASA, aspirin; IM, intramuscular; IV, intravenous; Cox, cyclo-oxygenase enzyme.

Table 3 Meta-analysis of NSAIDs versus placebo in LBP by the Cochrane Collaboration 2011

Comparison: analysis NSAIDs versus placebo***	Condition Acute LBP* Chronic LBP**	Number of patients (NSAID)	Placebo	Mean difference IV, random, 95% CI	Test for overall effect: Z
Change in pain intensity from baseline on 100 mm VAS	Acute LBP	375	370	− 8.39 [−12.68, −4.10]	3.84 (P = 0.00013)	Favors NSAIDs
Proportion of patients experiencing global improvement	Acute LBP	476	478	1.19 [1.07, 1.33]	3.28 (P = 0.0010)	Favors NSAID
Proportion of patients experiencing side effects	Acute LBP	907 (total events = 150)	945 (total events = 116)	1.35 [1.09, 1.68]	2.74 (P = 0.0061)	Favors placebo
Additional analgesic use	Acute LBP	462 (total events = 208)	436 (total events = 246)	0.80 [0.71, 0.91]	3.44 (P = 0.00058)	Favors NSAID
Change in pain intensity from baseline on 100 mm VAS LBP without sciatica	Acute LBP	289	288	−7.69 [−12.08, −3.30]	3.43 (P = 0.00059)	Favors NSAIDs
Change in pain intensity from baseline on 100 mm VAS LBP with sciatica	Acute LBP	291	274	−0.16 [−11.92, 11.59]	0.03 (P = 0.98)	No significance
Change in pain intensity from baseline on 100 mm VAS (mixed population)	Acute LBP	86	82	−23.40 [−43.67, −3.13]	2.26 (P = 0.024)	Favors NSAIDs
Change in pain intensity from baseline on 100 mm VAS	Chronic LBP	512	508	−12.40 [−15.53, −9.2]	7.75 (P < 0.00001)	Favors NSAID
Proportion of patients experiencing side effects	Chronic LBP	519 (total events = 242)	515 (total events = 195)	1.24 [1.07, 1.43]	2.95 (P = 0.0032)	Favors placebo
NSAIDs versus paracetamol, pain intensity on various scales	Acute LBP	151	158 (paracetamol)	−0.21 [−0.43, 0.02]	1.80 (P = 0.071)	Favors NSAIDs
NSAIDs versus paracetamol, proportion of patients experiencing global improvement	Acute LBP	65 (total events = 36)	63 (paracetamol) (total events = 28)	1.23 [0.88, 1.73]	1.22 (P = 0.22)	Favors NSAID
NSAIDs versus paracetamol, proportion of patients experiencing side effects	Acute LBP	152 (total events = 33)	157 (paracetamol) (total events = 19)	1.76 [1.12, 2.76]	2.45 (P = 0.014)	Favors paracetamol
NSAIDs selective Cox-2 inhibition versus nonselective, change in pain intensity from baseline on 100 mm VAS	Acute LBP	383	378	−1.17 [−4.67, 2.33]	0.65 (P = 0.51)
NSAIDs selective Cox-2 inhibition versus nonselective, change in pain intensity from baseline on 100 mm VAS	Chronic low back pain	222	218	2.00 [−1.92, 5.92]	1.00 (P = 0.32)	Favors Cox-2 selective
NSAIDs selective Cox-2 inhibition versus nonselective, proportion of patients experiencing side effects	Acute low back pain	216 events = 49 (Cox-2 selective)	212 events = 56 (non selective)	0.86 [0.62, 1.20]	0.89 (P = 0.37)	Favors Cox-2 selective
NSAIDs selective Cox-2 inhibition versus nonselective, proportion of patients experiencing side effects	Subacute chronic low back pain	93 events = 26 (Cox-2 selective)	98 events = 41 (nonselective)	0.67 [0.45, 1.00]	1.97 (P = 0.049)	Favors Cox-2 elective
NSAIDs selective Cox-2 inhibition versus nonselective, proportion of patients experiencing side effects	Chronic low back pain	222 events = 79 (Cox-2 selective)	218 events = 87 (nonselective)	0.89 [0.70, 1.13]	0.93 (P = 0.35)	Favors Cox-2 selective
NSAIDs selective Cox-2 inhibition versus nonselective, proportion of patients experiencing side effects	Chronic low back pain	531 events = 154 (Cox-2 selective)	528 events = 184 (nonselective)	0.83 [0.70, 0.99]	2.03 (P = 0.042)	Favors Cox-2 selective
NSAIDs selective Cox-2 inhibition versus nonselective, proportion of patients experiencing gastrointestinal side effects	Acute low back pain	164 events = 17 (Cox-2 selective)	162 events = 19 (nonselective)	0.88 [0.48, 1.64]	0.39 (P = 0.69)	Favors Cox-2 selective
NSAIDs selective Cox-2 inhibition versus nonselective, proportion of patients experiencing gastrointestinal side effects	Chronic low back pain	222 events = 30 (Cox-2 selective)	218 events = 44 (nonselective)	0.67 [0.44, 1.02]	1.85 (P = 0.064)	Favors Cox-2 selective
NSAIDs selective Cox-2 inhibition versus nonselective, proportion of patients experiencing gastrointestinal side effects. Heterogenicity	Chronic low back pain	386 events = 47 (Cox-2 selective)	380 events = 63 (nonselective)	0.73 [0.52, 1.04]	1.74 (P = 0.083)	Favors Cox-2 selective

Notes:

* Acute LBP follow-up ≤3 weeks for acute LBP;

** chronic LBP follow up ≤12 weeks;

*** NSAIDs versus placebo or other compounds as described in the table.

Abbreviations: Cox, cyclo-oxygenase; LBP, low back pain; NSAIDs, nonsteroidal anti-inflammatory drugs; VAS, visual analog scale.