Drugs 2010; 70 (4): 387-402

0012-6667/10/0004-0387/$55.55/0

THERAPY IN PRACTICE

2010 Adis Data Information BV. All rights reserved.

Pharmacological Management of
Low Back Pain
Roger Chou
Departments of Medicine, Medical Informatics and Clinical Epidemiology, Oregon Health & Science
University, Portland, Oregon, USA

Contents
Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Evaluation of Low Back Pain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2. Pharmacological Management of Nonspecific Low Back Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1 Paracetamol (Acetaminophen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2 NSAIDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3 Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4 Tramadol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5 Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6 Skeletal Muscle Relaxants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.7 Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.8 Antiepileptic Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.9 Systemic Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.10 Other Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Abstract

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Low back pain is one of the most common conditions encountered in

clinical practice and medications are the most commonly used type of treatment. In most patients, low back pain is nonspecific, in that the pain cannot
be reliably attributed to a specific condition or abnormality in the back.
Although a number of medications are available to treat nonspecific low back
pain, selecting a therapy can be a challenge because each one is associated
with a unique set of benefits and harms. In addition, the evidence supporting
the use of different medications varies, and issues such as costs and patient
preferences may also affect treatment choices.
A guideline published in 2007 from the American Pain Society and the
American College of Physicians on diagnosis and treatment of low back pain
includes recommendations on the use of medications, based on the quality of
supporting evidence and the estimated magnitude of benefits relative to
harms. For most patients with low back pain, regardless of the duration of
symptoms, paracetamol (acetaminophen) and NSAIDs are first-line options
for pain relief. Opioids are more potent analgesics, but are not a first-line
option due to their abuse potential. Skeletal muscle relaxants and benzodiazepines can be used as adjunctive medications for acute low back pain, but
have a high incidence of sedation. Tricyclic antidepressants may be an option

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388

for chronic low back pain, but their effects on pain appear small or uncertain.
Nonetheless, depression is common in patients with low back pain and should
be treated appropriately.
When choosing medications for treatment of low back pain, practice
guidelines provide a useful starting point for making decisions, but clinicians
should base therapeutic choices on individualized consideration and discussion with patients regarding the potential benefits and risks.

Back pain is extremely common. In North

American and European studies, lifetime prevalence estimates range from 49% to 70%, with
point prevalences from 12% to 30%.[1] Back pain
is the fifth most common reason for office visits
in the US, and the second most common symptomatic reason, trailing only upper respiratory
infections.[2,3] Back pain can have a very negative
impact on quality of life, functional ability and
measures of general health, and is frequently associated with depression or anxiety.[4,5] In the US,
7 million adults are estimated to have activity
limitations due to chronic low back pain.[6]
Back pain is also costly. In 1998, total healthcare expenditures incurred by US individuals
with back pain were estimated at $US90 billion.[7]
The average healthcare costs for persons with
back and neck problems increased from $US4795
per year in 1997, to about $US6096 per year in
2005, an inflation-adjusted increase of 65%.[5] In
addition to the direct costs, indirect costs due to
lost time from work and decreased productivity
while at work are substantial.[8]
Many treatments are available for management
of low back pain.[9] Broadly speaking, treatments
for back pain can be categorized as pharmacological, non-pharmacological/non-interventional,
interventional and surgical. Of these, medications
are the most commonly used therapy and contribute significantly to the healthcare costs associated with low back pain care. In one study, 80%
of patients with low back pain seen in primary
care were prescribed or recommended at least one
medication at their initial office visit, and more
than one-third were prescribed two or more
medications.[10] Costs associated with prescription medications for low back pain more than
doubled between 1997 and 2005.[5]
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Selecting medications for low back pain can be

a challenge. Many medications are available,
with each associated with unique benefits and
harms. Until fairly recently, systematic reviews
identified only a handful of randomized trials
that evaluated the benefits and harms of medications for low back pain.[11] Fortunately, the
situation has improved, although research gaps
still remain. A guideline published in 2007 from the
American Pain Society (APS) and the American
College of Physicians (ACP) provides evidencebased recommendations on the evaluation and
management of low back pain.[9] This article reviews an evidence-based approach to the evaluation of low back pain, with a focus on how to
determine whether a patient has nonspecific low
back pain. It reviews the current evidence on
medications for nonspecific low back pain, highlighting recommendations from the APS/ACP
guideline, as well as key studies on low back pain
medications published after the guideline.
1. Evaluation of Low Back Pain
The differential diagnosis for low back pain is
broad. A small proportion of patients presenting
for initial evaluation have low back pain caused
by a specific disorder such as cancer (about 0.7%
of cases), spinal infection (0.01%), cauda equina
syndrome (0.04%), compression fracture (4%),
ankylosing spondylitis (0.35%), symptomatic
spinal stenosis (3%) or herniated disc with radiculopathy (4%).[12-14] Low back pain can also be a
symptom of a problem outside the back (such as
pancreatitis, nephrolithiasis, aortic aneurysm, or
systemic illnesses such as endocarditis or viral
syndromes). However, the great majority (around
85%) of patients who present to primary care
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Medications for Low Back Pain

have nonspecific low back pain.[15] This means

that the back pain cannot reliably be attributed to
a specific disease or spinal abnormality. Patients
with nonspecific low back pain may have degenerative disc disease, facet joint arthritis, bulging
discs or other imaging findings. The reason why
back pain in such people is referred to as nonspecific is because all of these findings correlate
poorly with the presence and severity of low back
pain.[15] There is no evidence that labelling the
back pain as originating from one of these anatomical sources helps guide therapeutic decisions
or improves outcomes, and no validated or reliable classification system exists. In fact, routine
imaging in patients with nonspecific low back
pain is not associated with better pain, functional
status or psychological outcomes compared with
usual care without routine imaging, but increases
the use of surgery and other invasive procedures,
and is a significant driver of increased costs.[16,17]
Nonspecific low back pain is in essence a diagnosis of exclusion. However, this does not
mean that an extensive work-up is necessary to
make the diagnosis. In fact, most patients do not
need imaging or other diagnostic tests. Rather,
the diagnosis of nonspecific low back pain is often based on the absence of historical or clinical
features suggesting a specific condition. In one
prospective study, no cases of cancer were found
in over 1000 patients without risk factors for
cancer.[12] Similarly, four randomized trials of
imaging strategies that enrolled nearly 400 patients without risk factors for serious conditions
(such as cancer, infection or cauda equina syndrome) found no missed cases.[16]
A practical approach to low back pain evaluation was outlined in the APS/ACP guideline.[9]
This approach built upon a framework presented
in earlier guideline efforts[18] and is similar to recommendations from the European Cooperation
in the Field of Scientific and Technical Research
(COST) Action B13 guideline.[19,20] Evaluation of
low back pain has two main goals: (i) to determine the likelihood that a specific condition is
causing the low back pain; and (ii) to determine
the presence and severity of neurological involvement. This helps place patients into one
of three categories: (i) nonspecific low back pain;
2010 Adis Data Information BV. All rights reserved.

389

(ii) back pain potentially associated with radiculopathy or spinal stenosis; or (iii) back pain potentially associated with another specific spinal
cause. Although broad, these categories are useful because they help guide subsequent diagnostic
and therapeutic decisions. Some specific conditions require urgent evaluation as they can lead to
severe or permanent complications (including
paralysis or permanent loss of function) if not
investigated and treated promptly. These include
tumours, infections and cauda equina syndrome,
or other severe or rapidly progressive neurological conditions. Other specific conditions are usually
less urgent, but are also important to identify
since they can result in different therapeutic decisions. For example, finding a new vertebral
compression fracture would typically lead to an
assessment of bone mineral density and secondary causes of osteoporosis, as well as treatments
to reduce the risk of future fractures. A new
diagnosis of ankylosing spondylitis could lead to
use of disease-modifying antirheumatic drugs.
Back pain with radiculopathy may respond to
different analgesic medications (due to the associated neuropathic component) and procedures
(such as epidural corticosteroid injections, discectomy or decompressive laminectomy) compared with nonspecific back pain.
The history should focus on risk factors for
specific conditions. A history of cancer (not
including nonmelanoma skin cancer) is the
strongest risk factor for spinal tumour (positive
likelihood ratio, 14.7).[12] Weaker risk factors are
unexplained weight loss, failure to improve after
1 month and age older than 50 years (positive
likelihood ratio 2.73.0). Based on these likelihood ratios, the probability of cancer would
increase from 0.7% in patients with back pain
presenting to primary care to approximately 9%
if a history of cancer is present. In patients with
any one of the other three risk factors, the posttest probability only increases to 1.2%. Features
that suggest a vertebral infection include fever,
intravenous drug use or recent infection.[13] Risk
factors for vertebral compression fracture include
a history of osteoporosis, corticosteroid use,
older age and female sex. Ankylosing spondylitis
should be considered in younger patients with
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390

chronic low back pain associated with morning

stiffness, improvement with exercise, alternating
buttock pain or awakening in the second part of
the night due to back pain.[21] For patients with
back and leg pain, a typical history of sciatica
(back and leg pain in a typical lumbar nerve root
distribution) has a fairly high sensitivity but uncertain specificity for a herniated disc, and spinal
stenosis is associated with older age and pain relieved by sitting.[22-25] For cauda equina syndrome, the key finding is new urinary retention.
In patients without urinary retention, the probability of cauda equina syndrome is about 1 in
10 000.[26]
The physical examination should focus on
evaluating for the presence and level of neurological involvement. In patients with back and leg
pain, a positive straight-leg-raise test (defined as
reproduction of the leg pain upon elevating the
leg on that side between 30 and 70) has a sensitivity of around 90%, but a specificity of only
about 25%, for herniated disc with radiculopathy.[26,27] A positive crossed straight-leg-raise
test (reproduction of the leg pain upon elevating
the opposite leg) is about 90% specific, but only
about 30% sensitive. More than 90% of symptomatic lumbar disc herniations occur at the L4/L5
or L5/S1 spine level, potentially causing radiculopathy due to compression of the nerve root.
Radiculopathy typically results in pain and sensory deficits in a nerve root distribution, and may
be associated with corresponding motor and reflex abnormalities. These are knee extension
strength and reflexes for the L4 nerve root, great
toe and foot dorsiflexion strength for the L5
nerve root, and foot plantarflexion strength and
ankle reflex for the S1 nerve root.
The APS/ACP guideline recommends that
clinicians perform imaging and other diagnostic
tests only in patients with severe or progressive
neurological deficits, or when a serious underlying condition is suspected based on the history
or physical examination.[9] Diagnostic testing is
also appropriate if vertebral compression fractures or ankylosing spondylitis are suspected.
Key features of the history and physical examination and the suggested work-up for specific conditions are shown in table I. In patients without
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these features, imaging and other diagnostic tests

are not recommended. Immediate imaging is also
not necessary for acute radiculopathy in the absence of severe or progressive neurological deficits, as patients typically improve in the first few
weeks, and initial management is similar to patients with nonspecific low back pain.[28,29]
It is also important to assess for risk factors
that may predict the development of persistent
or disabling low back pain.[30,31] These include
psychiatric co-morbidities, fear avoidance behaviours (avoiding recommended or normal activities because of fears they will damage the back)
and other maladaptive coping strategies, somatization, low general health status, and low job
satisfaction or disputed compensation claims. A
small proportion of patients with disabling back
pain account for the majority of costs associated
with low back pain.[32] Identification of those at
risk for persistent disabling back pain could help
identify patients who would benefit from more
frequent follow-up, care coordination, or use of
behavioural or other therapies to address psychosocial contributing factors. Such measures
have the potential to decrease the likelihood of
progression to persistent disabling low back pain,
although more research is needed to understand
optimal therapeutic strategies in high-risk patients. In terms of pharmacological management,
identification of psychiatric co-morbidities could
also help inform decisions about use of antidepressants or other psychiatric medications.
2. Pharmacological Management
of Nonspecific Low Back Pain
In patients deemed to have nonspecific low
back pain, a number of medications are available
as treatment options. The choice of medication
depends on a number of factors, including the
duration of symptoms, severity of symptoms,
expected benefits, prior response to medications,
adverse effect profile, presence of co-morbidities,
costs and degree of supporting evidence. Some
medications have only been shown to be effective
for acute (<4 weeks) back pain and others for
subacute (412 weeks) or chronic (>12 weeks)
back pain (table II). In general, the natural history
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391

Table I. Diagnostic evaluation of low back pain

Possible cause

Key features on history or physical

examination

Imaging

Additional studies

Cancer

History of nonmelanoma skin cancer

with new onset of low back pain
Unexplained weight loss
Failure to improve after 1 mo
Age >50 y with new or changed low
back pain

Lumbosacral radiograph or
MRI
Consider lumbosacral
radiograph, particularly with
multiple risk factors

ESR

Vertebral infection

Fever
Intravenous drug use
Recent infection

MRI, particularly with fever

and another risk factor

ESR and/or CRP

Cauda equina syndrome

New urinary retention

Faecal incontinence
Saddle anaesthesia

MRI (likelihood of cauda

equina syndrome 1 in 10 000
without new urinary retention)

None

Vertebral compression
fracture

History of osteoporosis
Use of corticosteroids
Older age (>65 y, women; >75 y, men)

Consider lumbosacral
radiograph

None

Ankylosing spondylitis

Symptoms for >3 mo

Morning stiffness
Improvement with exercise
Alternating buttock pain
Awakening due to back pain during the
second part of the night
Younger age (2030 y)
Male sex

Consider anterior posterior

pelvis radiograph if
symptoms present for >3 mo
and other risk factors present

HLA-B27

Severe/progressive
neurological deficits

Progressive lower extremity motor

weakness

MRI

Consider EMG/NCV

Herniated disc

Back pain with leg pain in an L4, L5 or

S1 nerve root distribution
Positive straight-leg-raise test or
crossed straight-leg-raise test

Symptoms present for <1 mo:

none
Symptoms present for >1 mo:
consider MRI

Symptoms present for <1 mo:

none
Symptoms present for >1 mo:
consider EMG/NCV testing

Spinal stenosis

Radiating leg pain

Older age (>65 y, women; >75 y, men)
Pseudoclaudication (note: weak
predictor)

Symptoms present for <1 mo:

none
Symptoms present for >1 mo:
consider MRI

Symptoms present for <1 mo:

none
Symptoms present for >1 mo:
consider EMG/NCV testing

CRP = C-reactive protein; EMG/NCV = electromyogram/nerve conduction velocity; ESR = erythrocyte sedimentation rate; HLA = human
leukocyte antigen.

of acute low back pain is quite favourable, with a

high likelihood of improvement in the first
month.[30,33] A short course of medications can
help patients get through the acute period, although no medication seems to alter the natural
course of low back pain episodes. Once back pain
has been present for longer than 12 weeks, the
likelihood of significant improvement drops
substantially. For chronic low back pain, medications may be used on a longer term and continuous basis or episodically, to treat acute
worsening or flares of back pain.
Other patient characteristics can also help inform medication choices. For example, patients
2010 Adis Data Information BV. All rights reserved.

with very severe pain may require stronger analgesics than those with milder pain. The criteria
used by the APS/ACP guideline to categorize
average expected benefits as small, moderate
or large compared with placebo are shown in
table III.[9] Unfortunately, no medication has
consistently been shown to result in large average
benefits on pain and evidence of beneficial effects
on function is even more limited. Nonetheless,
individual responses to medications can vary
substantially, even to different drugs from within
the same medication class. There is little research
on which patient characteristics can be used to
accurately predict responses to different drugs.
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Table II. Summary of evidence and recommendations on pharmacological therapies for low back pain from the American Pain Society and
American College of Physicians guideline on diagnosis and treatment of low back pain (see following tables for methods for estimating the
magnitude of benefit [table III], rating the quality of supporting evidence [table IV], and assigning an overall grade [table V])
Medication

Acute low back pain

Chronic or subacute low back pain

quality of supporting
evidence

estimated benefit

overall grade

quality of
supporting
evidence

estimated
benefit

overall
grade

Paracetamol
(acetaminophen)

Faira

Moderate

Bb

Faira

Small

B (minimal
harms)b

NSAIDs

Good

Moderate

Bb

Good

Moderate

Bb

Skeletal muscle
relaxants

Good

Moderate

Poor

Unable to
estimate

Tricyclic
antidepressants

No evidence

Unable to estimate

Fairc

Small to
moderate

B/C

Benzodiazepines

Fair

Moderate

Fair

Moderate

Tramadol,
opioids

Faira for opioids, no

evidence for tramadol

Moderate for opioids, unable

to estimate for tramadol

B for opioids,
I for tramadol

Faira

Moderate

Systemic
corticosteroids

Fair

Not effective

No evidence

Unable to
estimate

Antiepileptic
drugs

Poor

Unable to estimate

Poor

Unable to
estimate

Primarily indirect evidence.

First-line medication option.

Inconsistent results from systematic reviews.

However, an individuals prior response to a

specific drug is likely to be a useful predictor of
future response. The adverse effect profile of
different medications is also an important
consideration, particularly in patients with
significant co-morbidities or at higher risk for
adverse events. Costs and insurance coverage
can be a relevant factor when several medication
options appear similarly effective, or when
considering use of a newer drug or one without a
generic option.
The degree of supporting evidence for different medications varies. The method used by the
APS/ACP guideline to grade the evidence for
each intervention is shown in table IV. Factors
taken into consideration include the number, size
and quality of studies, and inconsistency between
studies. In some cases, assessments regarding efficacy must be extrapolated from trials conducted
in patients with other pain conditions, because
direct evidence or trials performed specifically
in people with low back pain are lacking. Although such extrapolations may be reasonable,
this type of evidence is indirect and therefore
considered weaker. In addition, it can be difficult
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to compare the relative benefits of medications

for low back pain because of the small number
of head-to-head trials and methodological limitations in some trials, including high loss to
Table III. Method for estimating magnitude of analgesic effects
Size of effect

Definition

Small/slight

Pain scales: mean 510 mm improvement on a

100 mm VAS, or equivalent
Back-specific functional status: mean 510 mm
improvement on the ODI, 12 points on the
RDQ or equivalent
All outcomes: SMD 0.20.5

Moderate

Pain scales: mean 1020 mm improvement on a

100 mm VAS or equivalent
Back-specific functional status: mean
1020 mm improvement on the ODI, 25 points
on the RDQ or equivalent
All outcomes: SMD 0.50.8

Large/substantial

Pain scales: mean >20 mm improvement on a

100 mm VAS or equivalent
Back-specific functional status: mean >20 mm
improvement on the ODI, >5 points on the RDQ
or equivalent
All outcomes: SMD >0.8

ODI = Oswestry Disability Index; RDQ = Roland-Morris Disability

Questionnaire; SMD = standardized mean difference; VAS = visual
analogue scale.

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Medications for Low Back Pain

Table IV. Method for grading the strength of evidence for an intervention
Grade

Definition

Good

Evidence includes consistent results from well designed,

well conducted studies in representative populations that
directly assess effects on health outcomes (at least two
consistent, higher-quality trials)

Fair

Evidence is sufficient to determine effects on health

outcomes, but the strength of the evidence is limited by the
number, quality, size or consistency of included studies;
generalizability to routine practice; or indirect nature of the
evidence on health outcomes (at least one higher-quality
trial of sufficient sample size; two or more higher-quality
trials with some inconsistency; at least two consistent,
lower-quality trials, or multiple consistent observational
studies with no significant methodological flaws)

Poor

Evidence is insufficient to assess effects on health

outcomes because of limited number or power of studies,
large and unexplained inconsistency between higherquality trials, important flaws in trial design or conduct, gaps
in the chain of evidence, or lack of information on important
health outcomes

follow-up or use of enrichment designs. Other

things being equal, medications with a more favourable balance of benefits relative to harms
and those supported by stronger evidence should
be prioritized over medications supported by
only weak evidence. The method used by the APS/
ACP guideline to grade each medication is
shown in table V. The grade is based on both
the strength of the evidence and the magnitude
of estimated benefit. Although the European

393

COST B13 guideline used different methods to

evaluate evidence, its recommendations on use of
medications are consistent with the APS/ACP
guideline.[19,20]
2.1 Paracetamol (Acetaminophen)

Paracetamol (acetaminophen) is an antipyretic

and analgesic medication without significant
anti-inflammatory properties. It is recommended
by the APS/ACP guideline as a first-line pharmacological option for low back pain of any
duration.[9] This recommendation is mainly
based on safety considerations and estimates of
efficacy derived from studies of other musculoskeletal pain conditions, as evidence on paracetamol specifically for low back pain is very
limited.[34,35] In fact, no trials have compared
paracetamol versus placebo for low back pain,
and the only trial that compared paracetamol to
no treatment found no beneficial effects in acute
low back pain.[36] Although five trials found no
clear difference in pain relief between paracetamol at dosages up to 4 g/day and different
NSAIDs for back pain of varying duration,[36-40]
paracetamol is usually considered a weaker analgesic than NSAIDs. Several higher-quality
systematic reviews of patients with osteoarthritis
(not limited to the back) consistently found
paracetamol slightly inferior to NSAIDs for pain

Table V. Method used by the American Pain Society and the American College of Physicians[9] to assign summary grades to each analgesic
medication
Summary grade Definition

Recommendation

The panel found good evidence that the intervention improves

health outcomes and concludes that benefits substantially outweigh
harms

The panel strongly recommends that clinicians

consider offering the intervention to eligible
patients

The panel found at least fair evidence that the intervention improves
health outcomes and concludes that benefits moderately outweigh
harms, or that benefits are small but there are no significant harms,
costs, or burdens associated with the intervention

The panel recommends that clinicians consider

offering the intervention to eligible patients

The panel found at least fair evidence that the intervention can improve The panel makes no recommendation for or
against the intervention
health outcomes, but concludes that benefits only slightly outweigh
harms, or the balance of benefits and harms is too close to justify a
general recommendation

The panel found at least fair evidence that the intervention is ineffective The panel recommends against offering the
or that harms outweigh benefits
intervention

Evidence that the intervention is effective is lacking, of poor quality or The panel found insufficient evidence to
conflicting, and the balance of benefits and harms cannot be determined recommend for or against the intervention

2010 Adis Data Information BV. All rights reserved.

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relief (standardized mean difference [SMD]

about 0.3).[41-43]
Although the magnitude of benefits associated
with paracetamol is probably only small, an important advantage of this medication is that it
also carries a low risk of serious harm. Unlike
NSAIDs, paracetamol is not known to be associated with myocardial infarction or gastrointestinal bleeding, and is better tolerated.[41,43]
Hepatotoxicity is the most serious harm associated with paracetamol and may occur even at
dosages near or at the currently recommended
maximum dosage (4 g/day).[44] In addition, inadvertent overdose may occur in patients who are
taking other medications that contain paracetamol.[45] As of October 2009, the US FDA is
considering a reduction in the maximum daily
recommended dose of paracetamol. In the meantime, clinicians should educate patients about the
potential for accidental overdose, avoid paracetamol in patients with pre-existing liver disease
or heavy alcohol use, and suggest using the lowest
effective daily dose.
2.2 NSAIDs

NSAIDs have anti-inflammatory and analgesic properties related to their ability to block the
cyclo-oxygenase (COX)-2 enzyme.[46] At the
same time, nonselective NSAIDs or NSAIDs
that block both the COX-1 and COX-2 enzymes
increase the risk for gastrointestinal bleeding,
because the COX-1 enzyme helps protect the
lining of the stomach from acid.
NSAIDs are also recommended as a first-line
medication option for either acute or chronic
low back pain.[9] A systematic review of randomized trials found that NSAIDs were effective for
short-term symptom relief, with average improvements of about 8 points (on a 0100 scale)
compared with placebo in patients with acute
back pain and about 12 points for chronic low
back pain.[35] The systematic review also found
strong evidence from 33 trials that different
NSAIDs, including both nonselective and COX-2
selective NSAIDs, are similarly effective. Factors
to consider when choosing a specific NSAID include response to prior NSAIDs (since response
2010 Adis Data Information BV. All rights reserved.

to individual NSAIDs may vary), adverse effect

profiles, costs and convenience (e.g. number of
doses per day). All NSAIDs are associated with
gastrointestinal and renal adverse effects, including serious harms such as bleeding ulcers
and upper gastrointestional perforation. A metaanalysis of 138 published and unpublished randomized trials found that both COX-2 selective
and nonselective NSAIDs were associated with
about a 2-fold risk of myocardial infarction compared with placebo.[47] Naproxen, a nonselective
NSAID, was the exception, with no apparent increased risk. However, these findings should be
interpreted cautiously, as some trials in the metaanalysis used supratherapeutic doses of NSAIDs
and a high proportion of cardiovascular events
occurred in patients prescribed NSAIDs for colonic adenoma prevention.[48] Cardiovascular
events were rare in most of the other trials, which
presents statistical challenges when pooling data.[49]
To minimize potential harms, cardiovascular
and gastrointestinal risk factors should be assessed before prescribing NSAIDs and the lowest
effective dose should be used for the shortest
period necessary. An American Geriatrics Society
guideline recommends against use of NSAIDs for
chronic pain in most adults aged >75 years due to
increased gastrointestinal and cardiovascular
risks,[50] and the American Heart Association
recommends avoiding NSAIDs for chronic pain
in persons with cardiovascular disease or at higher
cardiovascular risk.[51] However, long-term use
of alternative analgesics such as opioids is associated with serious risks related to the potential
for abuse, addiction and other adverse effects.
Because the risks of different medications vary
from patient to patient, the decision to use
NSAIDs or an alternative analgesic should be
individualized. If an NSAID is used in a patient
at higher risk for drug-related complications,
steps can be taken to help mitigate risks. To reduce gastrointestinal risk, clinicians can prescribe
the NSAID with a proton pump inhibitor or
misoprostol, or prescribe a COX-2 selective
NSAID.[52] Although celecoxib is the only COX-2
selective NSAID approved for use in the US,
etoricoxib and parecoxib are available in Europe.
Naproxen or aspirin may be the most appropriate
Drugs 2010; 70 (4)

Medications for Low Back Pain

NSAIDs in patients at higher cardiovascular risk,

the latter because of its platelet inhibition effects.[51]
2.3 Opioids

The use of opioids for low back pain remains

controversial. Opioid analgesics are derivatives
of morphine that bind to opioid receptors. Some
are available in immediate- and sustained-release
formulations, and opioids can be administered
via a variety of routes (most commonly oral or
transdermal). While opioids are considered the
most potent class of analgesics, they are also associated with serious harms, including respiratory
depression (which can be due to accidental overdose) and harms related to their abuse and addiction potential.
The APS/ACP guideline recommends the judicious use of a time-limited course of opioids in
patients with severe, disabling low back pain not
controlled (or unlikely to be controlled) with
paracetamol and NSAIDs.[9] Opioids are also an
option in patients with moderate or severe pain at
high risk of complications due to NSAIDs.[50,51]
Because of substantial risks, the potential benefits and harms of opioid analgesics should be
carefully weighed before an initial trial of therapy. Decisions regarding long-term opioid treatment for persistent low back pain should be based
on the response to an initial trial of opioids and
ongoing assessment of signs of misuse, abuse and
adverse effects. The APS and the American
Academy of Pain Medicine published guidelines
in 2009 on use of opioids for chronic noncancer
pain that can help guide clinical decision-making
regarding this class of drugs.[53]
Evidence on benefits of opioids specifically for
low back pain is limited. In fact, two systematic
reviews of opioids for low back pain identified
few high-quality or long-term trials, with limited
evidence that opioids reduce pain compared with
placebo or nonopioid analgesics.[54,55] However,
two trials published after the guideline found a
long-acting opioid moderately to substantially
(1723 points on a 100-point pain scale) more
effective than placebo for chronic low back
pain.[56,57] Knowledge about the effects of opioids
on other pain conditions might also be extra 2010 Adis Data Information BV. All rights reserved.

395

polated to low back pain. Opioids are widely recognized as the most potent analgesics for most
types of severe acute pain presumably acute low
back pain should respond similarly. For chronic
pain in general, systematic reviews consistently
found opioids moderately effective for pain relief
compared with placebo (a mean improvement in
pain of about 30% or an SMD for pain relief of
-0.60), although effects on functional outcomes
were small.[58,59]
For acute, short-term use, short-acting opioids
are generally recommended. For more long-term
use, long-acting, around-the-clock dosing has
often been suggested because it results in more
consistent blood concentrations. This could potentially reduce euphoric effects (which may correlate with the risk for abuse) and be associated
with more consistent pain relief. However, there
is no evidence that long-acting, around-the-clock
dosing is more effective than short-acting or asneeded dosing,[60] and continuous exposure to
opioids could induce tolerance and lead to dose
escalations, with attendant endocrinological and
other adverse effects. Although use of longacting, around-the-clock opioids may be a reasonable goal in most patients who are on long-term
opioid therapy, there is no compelling reason to
switch over patients who are doing well on a
short-acting, as-needed regimen.[53]
Opioids are commonly associated with adverse
effects, including constipation, nausea, somnolence, pruritus and myoclonus.[61] The strongest
and most consistent predictors for opioid abuse
are a personal or family history of substance
abuse.[62] However, reliable estimates of risks for
abuse and addiction are not available. One systematic review found aberrant drug-taking behaviours in up to 24% of patients receiving
opioids for low back pain, but estimates varied
and most studies had important methodological
shortcomings, including poorly described or
poorly validated methods for identifying aberrant
drug-related behaviours.[55] In addition, most
clinical trials excluded patients at higher risk for
abuse or addiction. In general, less serious aberrant drug-related behaviours (such as losing a
prescription, mild dose escalations and occasional unauthorized extra doses) seem to be much
Drugs 2010; 70 (4)

Chou

396

more common than overt abuse or addiction.

Several new abuse-deterrent and abuse-resistant
formulations of opioids are currently under review by the FDA, although none are yet commercially available.[63] Whether these formulations succeed in actually reducing opioid misuse
and abuse in clinical practice remains to be seen.
2.4 Tramadol

Tramadol is a synthetic centrally active analgesic that has weak affinity for opioid a-receptors.
It is an option in patients with nonspecific low
back pain, although not recommended as a firstline medication because of relatively limited evidence, no clear advantages over NSAIDs, and
some potential for abuse.[9] For chronic low back
pain, one meta-analysis found that tramadol was
minimally more effective than placebo for improving function (SMD 0.17; 95% CI 0.04, 0.30)
and moderately more effective for pain relief
(SMD 0.71; 95% CI 0.39, 1.02) in three trials.[54]
A recent trial not included in the meta-analysis
found that tramadol was minimally more effective than placebo for both pain (by 610 points
on a 100-point scale) and function (by 1.31.6
points on the 024 Roland Disability Questionnaire).[64] In head-to-head trials, the benefits of
tramadol were similar to those of NSAIDs or
weak opioids.[65,66] In terms of tolerability, tramadol was associated with similar rates of withdrawal due to adverse events compared with
placebo or the combination of paracetamol plus
codeine.[66,67] Although tramadol is not a federally controlled substance in the US, there are
many case reports of abuse and withdrawal.[68]
Tramadol is also associated with the serotonin
syndrome, which can occur when it is used in
combination with certain antidepressants.
2.5 Antidepressants

Therapeutic effects of antidepressants on depression are thought to be due to their effects on

various neurotransmitters. Certain antidepressants
(especially those that inhibit norepinephrine uptake) are also thought to have pain-modulating
properties independent from their effects on depression.[69] In particular, tricyclic antidepressants
2010 Adis Data Information BV. All rights reserved.

(TCAs) have long been used to treat various

chronic pain syndromes.
TCAs are an option for chronic low back pain,
but not recommended as first-line therapy because
of small or questionable benefits and known
adverse effects.[9] Several meta-analyses on the
effect of antidepressants versus placebo for shortterm therapy of chronic nonspecific low back
pain reported conflicting results.[70-72] Two metaanalyses found TCAs slightly more effective than
placebo for low back pain relief,[70,71] with an
estimated SMD of 0.41 (95% CI 0.22, 0.61) for
pain relief, but no difference in activities of daily
living.[70] A more recent meta-analysis published
after the guideline, differing from the earlier studies in the selection criteria used, trials included
and methods for analysing results, found no difference between antidepressants and placebo for
relief of pain or depression.[72] A factor that
complicates interpretation of these discrepant
systematic reviews is that some of the trials included in the meta-analyses had methodological
shortcomings, including baseline differences between randomized groups.[73,74] No trial has
evaluated the use of TCAs for acute low back
pain.
Antidepressants are associated with a higher
risk of adverse events (most commonly drowsiness, dry mouth and dizziness) compared with
placebo.[70] If a TCA is used, tertiary amine TCAs
(such as amitriptyline and imipramine) are associated with a higher frequency of these adverse
effects than secondary amines (such as nortriptyline and desipramine). TCAs are also associated
with ECG QRS prolongation and arrhythmias,
although the risk is probably small in the relatively low doses commonly used for treatment of
pain.
Selective serotonin reuptake inhibitors and
trazodone have not been shown to be effective for
low back pain.[70,71] Serotonin norepinephrine reuptake inhibitors such as venlafazine, duloxetine
and milnacipran demonstrate benefits for certain
types of chronic pain,[75,76] but have not been
studied for low back pain, either with or without
a neuropathic component.
Although antidepressants are not a first-line
medication option for treatment of back pain
Drugs 2010; 70 (4)

Medications for Low Back Pain

itself, depression is common in patients with

chronic low back pain and should be assessed and
treated appropriately.[4] In one study, only about
one-third of patients with chronic low back pain
who screened positive for depression were taking
antidepressant medications.[77]
2.6 Skeletal Muscle Relaxants

The term skeletal muscle relaxants refers to a

diverse collection of pharmacologically unrelated
medications, grouped together because they are
approved by regulatory agencies for treatment
of spasticity or for musculoskeletal conditions
such as tension headache or back pain. In the US,
skeletal muscle relaxants approved for treatment
of spasticity are baclofen, dantrolene and tizanidine;
those approved for treatment of musculoskeletal
conditions are carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol and
orphenadrine. Skeletal muscle relaxants that are
available outside the US include tolperisone,
thiocolchicoside, flupirtine and eperisone. Baclofen blocks pre- and post-synaptic GABAB receptors, tizanidine is a centrally acting agonist of
a2-adrenoceptors, dantrolene decreases the release of calcium from skeletal muscle sarcoplasmic reticulum, cyclobenzaprine is closely
related to TCA antidepressants, carisoprodol is
metabolized to meprobamate, methocarbamol is
structurally related to mephenesin, chlorzoxazone is a benzoxazolone derivative, and orphenadrine is derived from diphenhydramine. Other
than dantrolene, which directly inhibits muscle
contraction, it is not clear whether these medications truly relax muscles, or if their effects are
related more to sedation or other nonspecific
effects.
Skeletal muscle relaxants are an option for
acute nonspecific low back pain, although not
recommended as first-line therapy because of a
high prevalence of adverse effects.[9] A systematic
review of 30 trials found skeletal muscle relaxants
moderately superior to placebo for short-term
pain relief.[78] The relative risks for not achieving
pain relief (at least a 2-point improvement on an
11-point pain rating scale) were 0.80 (95% CI
0.71, 0.89) at 24 days and 0.67 (95% CI 0.13,
2010 Adis Data Information BV. All rights reserved.

397

3.44) at 57 days. There was insufficient evidence

to determine whether any skeletal muscle relaxant was superior to any other. Tizanidine was the
only antispasticity skeletal muscle relaxant well
studied for low back pain.[78,79] There was insufficient evidence to determine whether skeletal
muscle relaxants are effective for chronic low
back pain.
Skeletal muscle relaxants are associated with
more CNS adverse events (primarily sedation)
than placebo (relative risk [RR] 2.04; 95% CI
1.23, 3.37).[78] One trial of cyclobenzaprine showed
that sedative adverse effects were lower at doses
of 5 mg three times daily compared with 10 mg
three times daily, with comparable efficacy.[80]
Similar data on benefits and harms at different
doses are not available for other skeletal muscle
relaxants. Although reliable evidence on comparative risks is lacking, the risk-benefit profiles
of different skeletal muscle relaxants could theoretically vary substantially because they are
pharmacologically quite different. For example,
carisoprodol is metabolized to meprobamate, a
controlled substance in the US because of its
abuse and addiction potential. Because there is
no evidence of increased efficacy of carisoprodol
over other skeletal muscle relaxants, this drug
should be avoided based on the potential harms.
In fact, the European Medicines Agency issued a
recommendation to suspend marketing of all
carisoprodol-containing products in late 2007.[81]
Dantrolene should not be used for low back pain
because it carries a black box warning for potentially fatal hepatotoxicity and has not been
shown to be effective for musculoskeletal conditions. Both tizanidine and chlorzoxazone are associated with hepatotoxicity that is usually not
serious and generally reversible.[79]
The addition of a skeletal muscle relaxant to
paracetamol or an NSAID may be more effective
than the analgesic alone. Three trials found that
combination therapy was superior to monotherapy with paracetamol or an NSAID for
short-term pain relief.[82-84] However, as might
be expected, the addition of a skeletal muscle relaxant also increased the risk of sedation and
other CNS adverse effects (RR 2.44; 95% CI 1.0,
5.6).[78]
Drugs 2010; 70 (4)

Chou

398

2.7 Benzodiazepines

Benzodiazepines are a class of medications

that act on GABAA receptors and have sedative,
anxiolytic and antiepileptic effects. They are often used as skeletal muscle relaxants, but are not
approved by the FDA for this indication. Benzodiazepines may be best considered as an alternative to skeletal muscle relaxants, with relatively
limited evidence on efficacy and some potential
for abuse.[9] For acute low back pain, evidence on
efficacy of benzodiazepines versus placebo is
mixed, with one trial showing no benefit[85] and
another showing short-term pain relief.[86] On the
other hand, several randomized trials showed no
difference between various benzodiazepines and
skeletal muscle relaxants for acute low back pain,
suggesting comparable benefit.[78] Data on the
effectiveness of benzodiazepines for subacute or
chronic low back pain are also limited, with some
trials showing no benefit.[87-89] Adverse effects of
benzodiazepines are primarily related to their
sedative effects. If benzodiazepines are used, a
short, time-limited course of therapy is recommended to minimize the potential for abuse or
addiction.
2.8 Antiepileptic Medications

There is insufficient evidence to recommend

antiepileptic medications for treatment of nonspecific low back pain. One randomized trial in a
mixed population of patients with chronic low
back pain with or without radiculopathy found
topiramate moderately superior to placebo for
pain relief, but only slightly superior for functional improvement.[90] Other trials of antiepileptic drugs (gabapentin and topiramate)
focused on patients with radiculopathy or spinal
stenosis, with some trials showing no or small
benefits.[91-94]
2.9 Systemic Corticosteroids

Systemic corticosteroids are not recommended

in patients with nonspecific low back pain.[9] A
randomized trial of patients with acute nonradicular low back pain found no difference in
pain relief over 1 month between a single intra 2010 Adis Data Information BV. All rights reserved.

muscular injection of methylprednisolone 160 mg

and placebo.[95] Other trials of systemic corticosteroids that focused on patients with sciatica also
demonstrated no benefit.[96-98]
2.10 Other Medications

Anti-tumour necrosis factor (TNF)-a therapy,

which is primarily used in the treatment of inflammatory rheumatological and bowel disease,
does not have an established role for low back
pain. The only randomized trial evaluated patients with lumbar radiculopathy.[99,100] This
found no difference between infliximab and a
saline infusion at 3-month or 1-year follow-up.
Tanezumab is the first drug in the anti-nerve
growth factor antibody class to be evaluated in
clinical trials for chronic low back pain. A phase
II trial (published only as a conference abstract as
of November 2009) showed that a single intravenous infusion of tanezumab was superior to
both naproxen and placebo for achieving 50%
pain relief over 12 weeks (57% vs 34% vs 20%,
respectively) and improving Roland-Morris Disability Questionnaire scores (mean -7.7 vs -4.7 vs
-3.9, respectively), but was also associated with
an increased risk of altered peripheral sensation (e.g. paraesthesias, hyperaesthesias or dysaesthesias), possibly related to nerve injury.[101]
Although most events were reported as mild or
moderate, more studies are needed to understand
the frequency and severity of adverse events with
tanezumab.
3. Conclusions
An approach to low back pain that assesses for
risk factors that suggest a serious or other specific
underlying condition (such as cancer, infection or
compression fracture), determines the presence
and degree of neurological symptoms or compromise, and identifies findings associated with
prolonged or delayed recovery can help guide
diagnostic and management decisions. Most
(>85%) of patients will have back pain without an
identifiable, specific cause in other words,
nonspecific low back pain.
Drugs 2010; 70 (4)

Medications for Low Back Pain

For nonspecific low back pain, several medications are effective for short-term relief of acute
or chronic symptoms, although each is associated
with a unique set of risks and benefits. Regardless
of which medication is chosen, patients should be
counselled about the small to moderate average
expected benefits, in order to avoid unrealistic
expectations of efficacy. In addition, evidence is
limited on the benefits and harms associated with
long-term use of medications for low back pain.
Therefore, extended courses of medications
should be reserved for patients clearly showing
continued benefits from therapy without major
adverse events. Additional research is needed to
better understand how benefits and harms of
different medications compare with one another,
the optimal sequencing of medications, and
whether and how different medications should be
combined.
The APS/ACP guideline recommends paracetamol and NSAIDs as first-line medication
options. However, each class of medication is
associated with unique trade-offs involving benefits, risks and costs. Although the recommendation provides a useful framework to guide
pharmacological therapy, decisions must be individualized, as the relevant trade-offs will vary
depending on specific patient circumstances.[9]
For example, in a patient with mild or moderate
pain, a trial of paracetamol is a reasonable first
option because it offers a more favourable safety
profile than NSAIDs or opioids, even though it is
a relatively weak analgesic. For more severe pain,
some individuals might consider a small increase
in cardiovascular or gastrointestinal risk with
NSAIDs an acceptable trade-off for increased
analgesia, although other patients might consider
even a small increase in these risks to be unacceptable. For very severe, disabling pain or in
patients at high risk for NSAID-related complications,[50,51] a trial of opioids may be a reasonable option in appropriately selected individuals.
Medications such as skeletal muscle relaxants
and tricyclic antidepressants can be considered
alternative or adjunctive medications for acute or
chronic low back pain, respectively, but are not as
suitable as first-line options because of adverse
effects and (in the case of TCAs) small or un 2010 Adis Data Information BV. All rights reserved.

399

certain benefits. As in other medical decisions,

clinicians should base therapeutic choices on
individualized consideration and discussion with
patients regarding the potential benefits and risks.
Acknowledgements
No sources of funding were used to assist in the preparation of this article. The author has no conflicts of interest that
are directly relevant to the content of this article.

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Correspondence: Dr Roger Chou, 3181 SW Sam Jackson Park

Road, Mail Code: BICC, Portland, OR 97239, USA.
E-mail: chour@ohsu.edu

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