Chou et al. (2007a) summarized several key points
regarding the prevalence, etiology, and classification of neuropathic
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Start at 300 mg, titrate to 900 mg, increase up to
1,800 mg (in three doses)
900–3,600 mg (1,800 mg)
Start at 150 mg, increase up to 300 mg (in two to three
75–600 mg (300 mg)
60 mg once daily
20–120 mg (90 mg)
Lidocaine 5% patch
Up to three patches for up to 12 hours within a 24-hour
Note. NA = not
applicable; RCTs = randomized, controlled trials; SNRI = serotonin–norepinephrine
Crofford et al. 2005
Mean pain score
Arnold et al. 2007cb
Arnold et al. 2004
Fibromyalgia Impact Questionnaire (total and
Arnold et al. 2005
Brief Pain Inventory (average pain severity)
Russell et al. 2008
Patient Global-Rated Improvement
Gendreau et al. 2005
Pain intensity (pain diary) Average daily pain score
Clauw et al. 2007bb
Composite (pain severity plus global improvement plus
Clauw et al. 2007ab
Composite (pain severity plus global improvement)
Arnold et al. 2007a
Note. SNRI = serotonin–norepinephrine
duloxetine are U.S. Food and Drug Administration (FDA)–approved
for the treatment of fibromyalgia. It is expected that applications
for FDA approval of milnacipran will be submitted in 2009.
in abstract form but not yet published.
Most back pain (>70%–80%)
improves in the first 2–6 weeks. Thus, a 4-week wait (i.e.,
a conservative approach) is warranted (even with sciatica) in the
absence of red flags.
Red flags that may prompt earlier diagnostic testing
or referral include the following:
Cancer: history of cancer (strong predictor) or unexplained
weight loss, failure to improve after 4 weeks, and age greater than
50 years (all weaker predictors)
Infection (vertebral): fever, intravenous drug use, recent
infection (none well studied)
Compression fracture: older age, osteoporosis, steroid use
Cauda equina syndrome rare (0.04%); urinary retention
Physical examination focuses on a few cardinal neurological
parts of the lower-body exam:
Straight-leg raising (SLR) in which the hip is flexed while
the knee remains extended. Ipsilateral-positive SLR is 91% sensitive but
only 26% specific for radiculopathy, whereas a crossed-positive
SLR (i.e., sciatica in the other leg) is only 29% sensitive but
Lower-extremity motor and sensory exam:
Knee strength and reflexes (L4 nerve root); screen with
squat and rise
Great toe and foot dorsiflexion strength (L5 nerve root);
screen with heel walking
Foot plantar-flexion and ankle reflexes (S1 nerve root);
screen with walking on toes
Diagnostic tests are needed in only a minority of cases
(with red flags or persistent neurological signs).
MRI is the preferred imaging study (less radiation and better
visualization of soft tissue, vertebral marrow, and the spinal canal).
With some weaker red flags (e.g., age >50
years), plain films and ESR may be obtained first and MRI obtained
only if these tests are abnormal or symptoms persist.
Psychological factors are a stronger predictor of chronicity
and functional outcomes such as disability than physical exam findings or
the severity or duration of pain.
Treatment: No treatment for back pain has good-quality
(grade A) evidence of substantial benefit. The following have fair-quality (grade
B) evidence of moderate benefit or small benefits but no significant
harm, costs, or burdens:
Pharmacotherapy: acetaminophen, NSAIDs, TCAs, tramadol/opiates,
Nonpharmacological: chiropractic, acupuncture, massage, yoga,
exercise, progressive relaxation, cognitive-behavioral therapy, intensive
Note. ESR = erythrocyte
sedimentation rate; MRI = magnetic resonance imaging; NSAIDs = nonsteroidal
anti-inflammatory drugs; TCAs = tricyclic antidepressants.
Vlad et al. 2007
Knee or Hip OA
Meta-analysis (15 trials, 2,825 patients)
Glucosamine hydrochloride (three trials) did not have
a significant effect size (0.06), but glucosamine sulfate (12 trials)
did (0.44). However, large heterogeneity among trials made conclusions
about efficacy uncertain.
Reichenbach et al. 2007
Meta-analysis (20 trials, 3,846 patients)
Minimal to no effect on symptoms. Only three large
high-quality trials, which accounted for 40% of patients.
Glucosamine and/or chondroitin
Distler and Anguelouch 2006
Review of prior reviews
Review of four prior meta-analyses and large GAIT trial concluded
that neither glucosamine nor chondroitin is effective in OA.
Samson et al. 2007
Systematic (21 trials)
Evidence from small trials inconclusive. The GAIT study in
1,583 patients showed no difference from placebo.
Hyaluronic acid (intra-articular)
Arrich et al. 2005
Meta-analysis (22 trials)
Small but clinically insignificant effect on pain.
Only four high-quality trials.
Systematic (42 trials)
Generally some modest benefits compared with placebo but
unclear clinical significance.
Note. GAIT = Glucosamine–Chondroitin
Arthritis Intervention Trial.