Home' Australian Pharmacist : Australian Pharmacist February 2012 Contents 108 Australian Pharmacist February 2012 I ©Pharmaceutical Society of Australia Ltd.
Lisa Nissen is Associate Professor (QUM),
at the School of Pharmacy, University of
Queensland and Deputy-Director, Centre
for Safe and Effective Prescribing (CSEP).
OLD DRUG NEW INDICATION
Gabapentin -- from epilepsy
By Associate Professor Lisa Nissen
The proportion of women in their
menopausal and postmenopausal years
is steadily growing as life expectancy
increases. With a significant proportion of
females aged over 50, most women will
live at least one third of their lives after
menopause. Menopause is a transition
between two times of life for women -- it's
not a disease or an illness. Menopause
occurs when a woman permanently stops
menstruating and is usually defined as not
having a menstrual period for 12 months.
All women will eventually experience
menopause, with the average onset
commonly occurring between the ages of
45 and 55 years.
Women experience a variety of symptoms as
a result of the hormonal changes associated
with menopause. These include mood
swings, insomnia, migraine, palpitations,
anxiety, depression, vaginal dryness,
urinary changes, bone loss, night sweats,
cardiovascular changes and hot flashes. Of
all these symptoms, hot flashes (sometimes
called hot flushes) are the most common
symptom experienced during menopause
affecting about 75% of women, and have
the most significant impact on quality of life.
Hot flashes occur most frequently in the first
two years of menopause.
Hot flashes are a momentary sensation
of flushing and extreme warmth, often
occurring in conjunction with palpitations
and anxiousness, followed by profuse
sweating and occasionally chills and
shaking. However, the frequency, duration,
and intensity of hot flashes vary from
woman to woman and also have a varying
impact on quality of life. When hot flashes
occur at night and are accompanied by
sweating, called night sweats, they can
interfere with sleep. The exact mechanism
of hot flashes is unknown. However, they
are vasomotor symptoms thought to be
associated with a lack of thermoregulation
in the hypothalamus due to oestrogen
withdrawal. It has also been suggested that
other centrally acting chemicals such as
adrenalin, dopamine, and serotonin (5-HT)
may be responsible for or associated with
the development of hot flashes.
Hormone therapy has long been recognised
as the primary treatment for hot flashes and
reduces their frequency in postmenopausal
women by 70--90%. However, the long-
term use of hormone therapy in healthy
postmenopausal women may lead to
increased risks of stroke, thromboembolic
events, heart disease, and breast cancer.
Given these increasing concerns other
non-hormonal pharmacologic alternatives
are necessary for the long-term treatment
of hot flashes. Several complementary
and alternative medicines including black
cohosh, chaste tree berry, dong quai,
ginseng, evening primrose oil, red clover
and soy extracts have been used by patients
for treating hot flashes. Non-hormonal
agents including clonidine, methyldopa,
propranolol, vitamin E and venlafaxine
have been used with varying benefits.
Venlafaxine to date has been the most
successful of these agents. More recently
a number of randomised controlled trials
have shown that gabapentin, an agent
originally marketed as an antiepileptic agent
can provide benefit for the management of
The mechanism by which gabapentin
exerts its effect in the treatment of hot
flashes is still unknown. It is thought that
it may be due its action in the adrenergic
and/or serotonergic pathways in the
pituitary hypothalamic region of the CNS.
Gabapentin was originally designed as a
lipophilic analogue of GABA, an inhibitory
amino acid in the central nervous system.
However, contrary to its original design
gabapentin has no affinity for GABA
receptors. Although the exact mechanism
of action for gabapentin is still to be
determined, it appears to have a unique
effect on voltage-dependent calcium
channels in postsynaptic dorsal horn
neurons. Gabapentin binds to the calcium
channel, blocking the influx of calcium
leading to a subsequent decrease in neuro-
excitation and neurotransmitter release.
Patients were given doses of gabapentin
ranging from 600--2,400 mg in divided doses
daily, starting off with a low dose of 300 mg
at night and titrating up. Gabapentin
significantly reduced hot flash composite
scores (45--71% from baseline) and the
frequency of the flashes. The most common
adverse effects experienced by patients
during the studies included: somnolence/
drowsiness, unsteadiness, and dizziness.
The adverse effects were most significant
in the first few weeks of treatment and
generally resolved after the first month of
treatment. Although the studies were short
(<12 weeks) and had relatively small sample
sizes their results showed that gabapentin
was a useful alternative treatment for hot
flashes. Gabapentin is not registered for this
indication in Australia.
• Hayes LP, Carroll DG, Kelley KW. Use of gabapentin for the
management of natural or surgical menopausal hot flashes.
Ann Pharmacother. 2011 Mar;45(3):388--94. Epub 2011 Feb 22.
• Aguirre W, Chedraui P, Mendoza J, Ruilova I. Gabapentin vs.
low-dose transdermal estradiol for treating post-menopausal
women with moderate to very severe hot flushes. Gynecol
Endocrinol. 2010 May;26(5):333--7.
• Yurcheshen ME, Guttuso T Jr, McDermott M, Holloway RG,
Perlis M. Effects of gabapentin on sleep in menopausal women
with hot flashes as measured by a Pittsburgh Sleep Quality
Index factor scoring model. J Womens Health (Larchmt). 2009
• Reddy SY, Warner H, Guttuso T, et al. Gabapentin, estrogen, and
placebo for treating hot flushes. A randomized controlled trial.
Obstet Gynecol 2006;108:41--48.
600--2,400 mg daily in divided doses
900--3,600 mg daily in divided doses
1800--3,600 mg daily in divided doses.
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