Download Gabapentin in the amelioration of neuropathic pain

Finecure Update
Gabafine
A Passi Publication
Gabapentin in the amelioration of neuropathic pain
Neuropathic pain
reflects significant progress over the past decade in elucidating the
mechanism of action of these drugs: a novel, specific action at one
of the subunits constituting voltage-sensitive Ca2+ channels.
Binding of these ligands to the alpha2delta subunit is considered to
explain their usefulness in treating several clinical disorders, including
epilepsy, pain from diabetic neuropathy, post-herpetic neuralgia and
fibromyalgia, and generalized anxiety disorder.3
Pain is an unpleasant sensation that originates from ongoing or
impending tissue damage. Management of different types of pain
(acute, postoperative, inflammatory, neuropathic or cancer) is the
most frequent issue encountered by clinicians and pharmacological
therapy is the first line of approach for the treatment of pain.1
Neuropathic pain is result of damage or dysfunction of periphery
or central nervous system. Peripheral mechanisms of neuropathic
pain include hyperexcitability of cell membrane and periphery
sensibilization. Central mechanism includes central sensibilization,
central reorganization of alpha-beta fibers and loss of inhibition
mechanisms.
The main symptoms of neuropathic pain are described as
lancinating, stabbing, or shooting pain. Hyperalgesia and allodynia
are special kind of neuropathic pain that is provoked by mechanic
or thermal stimuli. Mononeuropathy, plexopathy, radiculopathy, and
myelopathy, lesions of thymus, cortex or brain stem are real cause
of neuropathic pain.
The aim of treatment of patients with neuropathic pain is soothing
of pain and suffering and prevention of further development of the
pathological process. In the treatment of neuropathic pain drugs
such as opioid, nonsteroid antirheumatics, analgesics, tricyclic
antidepressants and antiepileptic agents are used. The most
successful treatment is with antiepileptic drugs of second generation.
Carbamazepine was the drug of choice till ten years ago. Since then
the leader position in treatment has belonged to gabapentin.2
gabapentin versus “the others” in Diabetic
painful neuropathy
Diabetic painful neuropathy (DPN) is one of the most common
causes of neuropathic pain. The management of DPN consists of
excluding other causes of painful peripheral neuropathy, maximising
diabetic control and using medications to alleviate pain.
Evidence from placebo-controlled studies has shown that opioids,
antiepileptic and antidepressant drugs together with capsaicin are
effective for alleviating DPN. Tramadol and oxycodone have been
shown to be effective in studies of limited duration but their adverse
effects, such as constipation and physical dependency, may limit their
usefulness as a first-line treatment for DPN. Of the antidepressant
drugs, the tricyclic antidepressants have been shown to be effective
for alleviating DPN. These medications are widely used but their
anticholinergic and sedative properties may not be well tolerated
by patients.
There is also good evidence that the serotonin-noradrenaline
reuptake inhibitor antidepressant drugs venlafaxine and duloxetine
are effective for treating DPN. However, venlafaxine may cause
cardiac dysrhythmias, and patients using this medication require
careful cardiac monitoring. Duloxetine appears to be less cardiotoxic
and is licensed in the US and EU for alleviating DPN.
The gabapentinoid group of drugs, gabapentin and pregabalin,
gabapentin is a novel modulator of
neurotransmission
The term ‘Ca2+ channel alpha2delta ligands’ has recently been
applied to an evolving drug class that includes gabapentin, and
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Finecure Update
may co-exist in an individual patient.
PHN occurs mainly in HZ patients 60
years of age and older, in particular in those
suffering from more severe acute pain and
rash. Administration of antiviral drugs
reduces the duration of pain associated
with HZ. The pathophysiology of PHN
may be distinctly different between
patients with either reduced or increased
skin sensitivity.
Therapy is with tricyclic drugs (e.g.,
nortriptyline), alpha 2 delta-ligands (e.g.,
gabapentin) or opiates with adjunctive
topical lidocaine or capsaicin.6
Treatment options for patients with diabetic peripheral neuropathic pain.
Gabapentin for
the treatment of
fibromyalgia
To assess the efficacy and safety of
gabapentin in patients with fibromyalgia, a
12-week, randomized, double-blind study
was designed to compare gabapentin
(1,200-2,400 mg/day) (n=75 patients)
with placebo (n=75 patients) for efficacy
and safety in treating pain associated
with fibromyalgia.
Gabapentin-treated patients displayed
a significantly greater improvement in the
Source: Argoff CE, Backonia M-M, Belgrade, MJ, Bennett GJ, Clark MR, Cole BE, et al. Consensus guidelines: treatment
Brief Pain Inventory (BPI) average pain
planning options. Mayo Clin Proc. 2006; 81[4 suppl]:S12-S25.
severity score. A significantly greater
proportion of gabapentin-treated patients
appear to be the most evidence-based of the antiepileptic drugs for
compared
with
placebo-treated
patients achieved response at end point
treating DPN. Large placebo-controlled studies have been performed
(51%
versus
31%;
P=0.014).
Gabapentin
compared with placebo also
with both of these agents. For many patients, it is still unclear what
significantly improved the BPI average pain interference score, the
advantages pregabalin has over gabapentin for DPN.4 Topiramate,
Fibromyalgia Impact Questionnaire total score, the Clinical Global
lamotrigine, sodium valproate and oxcarbazepine have been shown
Impression of Severity, the Patient Global Impression of Improvement,
to be effective in smaller studies but do not have the same evidence
the Medical Outcomes Study (MOS) Sleep Problems Index, and
base as the gabapentinoid group of drugs.
the MOS Short Form 36 vitality score, but not the mean tender
gabapentin for the treatment of Postpoint pain threshold or the Montgomery Asberg Depression
Rating Scale. Gabapentin was generally well tolerated. This study
herpetic neuralgia
showed that gabapentin (1,200-2,400 mg/day) is safe and efficacious
Herpes zoster episodes commence with a prodromal period of about
for the treatment of pain and other symptoms associated with
4 days with symptoms including pain and malaise. This is followed
fibromyalgia.7
by a rash lasting approximately 2-4 weeks, with possible subacute
herpetic neuralgia for up to 3 months, followed, in some patients,
gabapentin for the treatment of
by a period of post-herpetic neuralgia (PHN) lasting months or
Trigeminal neuralgia
possibly years. Severe acute pain is more likely in older females
5
Trigeminal neuralgia (TN) is reputed to be one of the most painful
and those with a prodrome or severe rash. Patients with herpes
conditions in human experience. Thus, many treatments, both
zoster experience severe pain and potential lasting complications
medical and surgical, have been developed for this relapsing and
such as post-herpetic neuralgia, ophthalmic disease/damage, and,
remitting, paroxysmal stabbing or electrical, facial pain syndrome.
rarely, skin complications (e.g., infection of rash area).
The likely etiology in many cases is vascular compression of the
Two separate mechanisms of PHN have been proposed: the first
trigeminal nerve root entry zone, leading to focal demyelination
is that the excitability of primary afferent neurons is increased after
and aberrant neural discharges. MRI may disclose neurovascular
nerve damage, causing irritable nociceptors and central sensitization,
contact, although not with sufficient sensitivity or specificity to
resulting in pain and allodynia; the second involves the degeneration
substitute for careful clinical diagnosis.
of nociceptive neurons, which leads to deafferentation with central
In treating TN, antiepileptic drugs are superior to traditional
hyperactivity, causing pain but without allodynia. Both mechanisms
Drug
GAbafine
Composition
Packing
Administration
Gabapentin 300 mg
10 x 10 Capsule
1 tds
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Finecure Update
analgesics. Carbamazepine is the first choice drug. Additional
drugs for which there is evidence of efficacy include oxcarbazepine,
baclofen, gabapentin, lamotrigine and phenytoin. The choice of
drug, whether or when to operate, and which procedure to choose
should be individualized to the particular needs and conditions of
the patient.8
Dr. K. S. Anand, DM
Senior Specialist & Head, Department of Neurology,
Dr. RML Hospital, New Delhi
Doctor opines...
Gabapentin has revolutionized the management
of neuropathic pain which was not possible
with such effectiveness before. In my
experience, the patients remain pain free while they are compliant
with the medication. I would rank Gabafine highly amongst all
the possible options available for managing neuropathic pain.
Gabapentin as a perioperative drug
Gabapentin was not, until recently, thought to be useful in acute
perioperative conditions. However, a growing body of evidence
suggests that perioperative administration is efficacious for
postoperative analgesia, preoperative anxiolysis, attenuation of
the haemodynamic response to laryngoscopy and intubation, and
preventing chronic post-surgical pain, postoperative nausea and
vomiting, and delirium.9
the effectiveness and safety of gabapentin combined with an opioid
versus opioid monotherapy for the management of neuropathic
cancer pain. Data obtained suggested that gabapentin added to
an opioid provides better relief of neuropathic pain in cancer
patients than opioid monotherapy; this combination of gabapentin
and an opioid may represent a potential first-line regimen for the
management of pain in these patients.11
Meta-analysis of gabapentin for perioperative pain control
Gabapentin, an anticonvulsant, has recently been suggested as an
effective postoperative ‘analgesic’ agent. Following the Quality
of Reporting of Meta-analyses recommendations, nine electronic
databases until February 2006 were searched, without language
restriction, for randomized controlled trials comparing gabapentin
with control for postoperative pain control.
Gabapentin caused a 35% reduction in total opioid consumption
over the first 24 h following surgery (ratio of means 0.65, 95% CI
0.59 to 0.72), a significant reduction in postoperative pain at rest (in
the first 24 h) and with movement (at 2 h, 4 h and 12 h), regardless
of whether treatment effects were expressed as ratios of means or
weighted mean differences, and a reduction of vomiting (relative
risk [RR] 0.73, 95% CI 0.56 to 0.95) and pruritus (RR 0.30, 95%
CI 0.13 to 0.70).10
Gabapentin reduces alcohol consumption
and craving
A randomized, double-blind, placebo-controlled trial was performed
in a Brazilian public outpatient drug treatment center, with 60 male
alcohol-dependent subjects with a mean age of 44 years and an
average of 27 years of alcohol use, who consumed 17 drinks per
day (165-170 g/day) over the past 90 days before baseline and
had no other significant medical or psychiatric condition.
After 28 days of treatment, the gabapentin group showed a
significant reduction in both number of drinks per day and mean
percentage of heavy drinking days, and an increase in the percentage
of days of abstinence, compared to the placebo group. These results,
together with the virtual absence of side effects and a favourable safety
profile, support gabapentin as a potential drug for the treatment of
alcohol withdrawal and dependence.12
Gabapentin/opioid combination versus
opioid alone for neuropathic cancer pain
Neuropathic cancer pain represents a major challenge. Treatment
often requires adjuvant analgesics, including gabapentin, to
complement the effects of opioids. This study aimed to compare
references
Highlights
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modulators of neurotransmission. Trends Pharmacol Sci. 2007 Feb; 28(2): 75-82.
4. Chong MS, Hester J. Diabetic painful neuropathy: current and future treatment options.
D rugs. 2007; 67(4): 569-85.
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managed? H erpes. 2007 Sep; 14 Suppl 2:30-4.
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2007 Nov; 68(11): 1691-700.
Gabapentin is effective in the treatment of chronic neuropathic
pain, trigeminal neuralgia and post-herpetic neuralgia.
A growing body of evidence suggests that perioperative
administration is efficacious for postoperative analgesia,
preoperative anxiolysis, attenuation of the haemodynamic
response to laryngoscopy and intubation, and preventing
chronic post-surgical pain, postoperative nausea and vomiting,
and delirium.
The potential availability of less expensive generic
formulations of gabapentin, together with greater experience
with its use, favour gabapentin as the main anti-epileptic
drug for alleviating DPN.
Gabapentin is safe and efficacious for the treatment of pain
and other symptoms associated with fibromyalgia.
Gabapentin improves the analgesic efficacy of opioids both
at rest and with movement, reduces analgesic consumption
and opioid-related adverse effects.
Gabapentin reduces alcohol consumption and craving, which
may help patients to maintain abstinence.
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