Download Suggestion from clinicians

Gabapentin
Addition to the List
Peer Feedback:
“Commonly used and studied for a variety of conditions such as neuropathic pain, hot flushes,
etc. with numerous clinical trials showing some degree of benefit; since neuropathic pain is so
difficult to treat, having another option seems warranted”
Literature Review Question:
What is the efficacy of gabapentin in treating neuropathic pain?
Literature Search:
eCPS - Neurologic Disorders: Neuropathic Pain
Cochrane
CPG via CMA
Pain Society Guidelines 2014
The gabapentinoids, gabapentin and pregabalin, bind to presynaptic voltage-gated calcium
channels in the dorsal horn, reducing the release of excitatory neurotransmitters such as
glutamate and substance P (21). These agents have been studied in large clinical trials, although
mainly in the management of painful diabetic neuropathy and postherpetic neuralgia. Gabapentin
has shown efficacy in three trials involving painful diabetic neuropathy and two trials involving
postherpetic neuralgia (22); however, four RCTs involving gabapentin have been negative,
including a trial of gabapentin in chemotherapy induced painful neuropathy (23-26). The
combined NNTs for gabapentin in the management of painful polyneuropathy and postherpetic
neuralgia were 6.4 and 4.3, respectively (27).
Pregabalin is an analogue of gabapentin, with the same mechanism of action, but it manifests
linear pharmacokinetics and has higher affinity for the presynaptic calcium channel. Four studies
have shown that pregabalin provides significant pain relief and improved quality of life in painful
diabetic neuropathy (28) and an additional four trials have shown efficacy in postherpetic
neuralgia (22). The combined NNTs for pregabalin in the management of painful diabetic
neuropathy and postherpetic neuralgia were 4.5 and 4.2, respectively (27). Pregabalin has also
been studied in chronic central NeP following spinal cord injury, with evidence of significant pain
relief (29,30). However, a study investigating pregabalin in the treatment of NeP associated with
chronic lumbosacral radiculopathy was negative (31), as was a recent trial involving refractory
painful diabetic neuropathy (32). A study investigating the safety and efficacy of pregabalin in
patients with central poststroke pain showed no significant improvement in the primary end point
of pain intensity; however, there were some improvements in secondary end points including
sleep and anxiety (33).
Gabapentin and pregabalin appear to be similar in their mechanisms of action and side-effect
profiles, and allow for more rapid titration than antidepressant agents. Pregabalin carries the
advantage of twice-daily dosing and linear pharmacokinetics relative to gabapentin.
Gabapentinoids in general have few drug interactions, but are dependent on renal excretion and,
therefore, require dosage reductions in patients with renal insufficiency (72).
Moulin, D. E., et al. "Pharmacological management of chronic neuropathic pain: revised
consensus statement from the Canadian Pain Society." Pain Research & Management: The
Journal of the Canadian Pain Society 19.6 (2014): 328.
Cochrane 2014
Gabapentin is a reasonably effective treatment for a variety of neuropathic pain conditions. It has
been demonstrated to be better than placebo across all studies for IMMPACT outcomes of
substantial and at least moderate improvement, producing almost identical results for all trials and
those in parallel-group studies lasting six weeks or longer. Numbers needed to treat to benefit
(NNTs) were between 5 and 7 for substantial and at least moderate improvement in PHN and
PDN. Results were consistent across the major neuropathic pain conditions tested, though
gabapentin was tested only in small numbers in uncommon neuropathic pain conditions and
fibromyalgia. The review concentrated on doses of gabapentin of 1200 mg daily or greater,
though a wide range of fixed doses and dose titration regimens were used.
Gabapentin was tested in nine different chronic pain conditions generally considered to be
neuropathic in origin, and three other chronic pain conditions where the aetiology may be different
(masticatory myalgia, CRPS-1, and fibromyalgia). For only three neuropathic pain conditions was
there sufficient information to be confident that it worked satisfactorily, namely PHN, PDN, and
mixed neuropathic pain, itself principally, though not exclusively, PHN and PDN.
Benefit was balanced by more withdrawals due to adverse events, and participants taking
gabapentin experienced more adverse events, including somnolence, dizziness, peripheral
oedema, and gait disturbance than did those taking placebo. Serious adverse events were no
more common with gabapentin than placebo, and death was an uncommon finding in these
studies.
There was no first tier evidence that was unequivocally unbiased. Second tier evidence, with
potentially important residual biases, showed that gabapentin at doses of 1200 mg or more was
effective for some people with painful neuropathic pain conditions. No evidence regarding a doseresponse effect was available for doses above 1200 mg daily, but limited evidence suggested
that doses lower than 1200 mg daily were less effective. The outcome of at least 50% pain
intensity reduction is regarded as a useful outcome of treatment by patients, and the achievement
of this degree of pain relief is associated with important beneficial effects on sleep interference,
fatigue, and depression, as well as quality of life, function, and work. About 35% achieved this
degree of pain relief with gabapentin, compared with 21% for placebo. Over half of those treated
with gabapentin will not have worthwhile pain relief. Results might vary between different
neuropathic pain conditions, and the amount of evidence for gabapentin in some conditions (all
except PHN, PDN, and mixed) is low, excluding any confidence that it works or does not work.
The level of efficacy found for gabapentin is consistent with the efficacy estimates for other drug
therapies in these conditions.
Moore, R. Andrew, et al. "Gabapentin for chronic neuropathic pain and fibromyalgia in
adults." The Cochrane Library (2014).
eCPS (2014)
Chronic Peripheral Neuropathic Pain
This category of neuropathic pain conditions includes postherpetic neuralgia, diabetic
neuropathy, causalgia (CRPS II), incisional neuralgias following mastectomy, thoracotomy or
bypass surgery, phantom limb pain and other neuropathies. Guidelines for the treatment of
chronic peripheral neuropathic pain have been developed by the Canadian Pain Society and
others.2 , 3 Tricyclic antidepressants (TCAs) and GABA derivatives such
as gabapentin and pregabalin are considered first-line agents (Figure 1 - Management of
Chronic Peripheral Neuropathic Pain3 , Table 5).
Until more is known about the safety of gabapentin or pregabalin, avoid these agents for the
treatment of neuropathic pain during pregnancy.13 , 14 Until more is known about the safety of
gabapentin or pregabalin, avoid these agents for the treatment of neuropathic pain while the
mother is breastfeeding.13 , 14
Table 5: Drug Therapy for Chronic Peripheral Neuropathic Pain
Class
GABA
Derivatives
Drug
Dose
Adverse Effects
gabapentin Initial:300–400
mg/day poin divided
doses
Neurontin, May increase at weekly
intervals to BID then
generics
TID
Maximum: 3600
mg/day
GABA
Derivatives
pregabalin
Lyrica,
generics
Initial: 50–150 mg
daily po in 2 divided
doses
Increase dose weekly
by 50–150 mg/day
Drug Interactions
Comments
Sedation, ataxia,
tremor; less
commonly, GI
upset, peripheral
edema, vision
changes, weight
gain.
Administration with
aluminum/magnesiumcontaining antacids
may decrease
bioavailability.
Not a Health $$
Canada–
approved
indication.
Sedation, ataxia,
edema, diplopia,
weight gain, dry
mouth.
No known significant
drug interactions.
BID dosing
is an
advantage.
Usual effective
dose:300–600 mg/day
Maximum: 600
mg/day
Legend:
$ < $25
$$ $25–50
Costa
$$$ $50–75
$$$$ $75–100
$$$$$ $100–125
Acute Neuropathic Pain—Herpes Zoster4
Early treatment of herpes zoster can reduce the severity of the infection; however, there is no
evidence that antivirals will prevent postherpetic neuralgia.6 Oral antivirals (acyclovir, famciclovir,
valacyclovir) are most effective if started within 72 hours of the onset of the rash. In addition to
$$
instituting an antiviral agent, it is important to relieve the acute pain. This may be accomplished
with early treatment with amitriptyline and/or gabapentin and if necessary opioids or nerve
blocks.
Neurologic Disorders: Neuropathic Pain; C. Peter N. Watson, MD, FRCPC; Date of revision:
October 2014