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OLD DRUG NEW INDICATION
Venlafaxine -- a sweet success
for diabetic neuropathy!
By Professor Lisa Nissen
Diabetic neuropathy is a type of nerve
damage that occurs as a consequence
of diabetes. It is a common and serious
complication of diabetes, yet it can be
prevented or its progression slowed with
a healthy lifestyle and tight blood glucose
control. Depending on the nerves affected,
the symptoms can range from pain and
numbness the extremities to problems with
the digestive system, urinary tract, blood
vessels and heart. For some people, these
symptoms are mild; for others, diabetic
neuropathy can be painful, disabling and
There are four main types of diabetic
neuropathy. Patients may have just
one type or symptoms of several types.
Most develop gradually, unfortunately
patients may not notice a problem until
considerable damage has occurred.
Peripheral neuropathy, the most common
form of the condition, generally affects the
feet and legs followed by the hands and arms.
Symptoms include: numbness, changes in
ability to feel pain or changes in temperature,
tingling or burning, feeling sharp, jabbing
pain that may be worse at night, pain when
walking, extreme sensitivity to the lightest
touch, muscle weakness and difficulty
walking, foot problems (e.g. ulcers infections).
Autonomic neuropathy, may affect other
organs, e.g. heart, bladder, lungs, stomach,
intestines, sex organs and eyes. Diabetes
can affect the nerves in any of these
areas, possibly causing: hypoglycaemia,
frequent urinary tract infections or urinary
incontinence constipation, uncontrolled
diarrhoea, nausea, vomiting and loss of
appetite, difficulty swallowing, erectile
dysfunction in men, sweating and
Radiculoplexus neuropathy, where instead
of affecting the ends of nerves, it affects
nerves in the thighs, hips, buttocks or legs.
Also called diabetic amyotrophy, femoral
neuropathy, or proximal neuropathy, this
condition is more common in people with
type 2 diabetes and older adults. Symptoms
include: sudden, severe pain in your hip
and thigh or buttock, eventual weak and
atrophied thigh muscles, difficulty rising
from a sitting position and weight loss.
Mononeuropathy involves damage to a
specific nerve. This condition is also called
focal neuropathy. Signs and symptoms
depend on which nerve is involved and may
include: difficulty focusing eyes, double vision
or aching behind one eye, paralysis on one
side of the face (Bell's palsy).
These neuropathies can cause a number of
serious complications, including the loss
of a limb because of damage or infections,
urinary tract infections, poor hypoglycaemic
awareness, blood pressure considerations,
digestive tract issues and sexual dysfunction.
Diabetic neuropathy has no known
cure. Treatment focuses on slowing the
progression of the disease, relieving pain,
managing complications and restoring
function. While many of these can be
achieved by optimising management of
blood glucose control, several medications
are used to relieve nerve pain. Among the
pain-relieving treatments that may be tried
are the following: Anti-seizure medications
(e.g. carbamazepine, gabapentin,
pregabalin) and antidepressants (e.g. TCAs
like amitriptyline), lignocaine patches and
opioids (e.g. tramadol, oxycodone). For many
people the side-effects of these older agents
Professor Lisa Nissen is the head of
the pharmacy school at Queensland
University of Technology.
are difficult to tolerate and as such newer
antidepressants like venlafaxine have been
suggested as alternatives.
Venlafaxine exerts its pharmacological action
as a serotonin and noradrenaline reuptake
inhibitor. It is postulated that its benefits
in the treatment of pain (vs depression)
come from modulation of the serotonin and
noradrenaline in the descending inhibitory
pain pathways. As such, the results of several
clinical trials (including open-label and
randomized placebo controlled trials) and
case series have indicated that venlafaxine
reduces the intensity and severity of pain
in patients treated. Overall in these studies,
the Numbers Needed to Treat (NNT) to
receive a 50% reduction in pain across the
trial populations varied, however generally
ranged between 3--5. Venlafaxine is generally
well tolerated, with the primary adverse
events being dry mouth, constipation,
decreased appetite, and nausea. Dosages
in clinical trials were similar to those used
commonly to treat depression with patients
starting on 75 mg daily and increasing slowly
to clinical benefit (Max 225 mg daily).
Venlafaxine currently has a TGA indication
for treating depression and more recently
anxiety disorders, however, it appears
to provide and alternative to traditional
antidepressants (TCAs) and opioid analgesics
for treating diabetic neuropathy.
Neuropathy Starting dose 75 mg daily
increase to 150 mg daily
(Max 225 mg)
and anxiety Starting dose 75 mg daily
increase to 150 mg daily
(Max 225 mg)
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Neurology; American Association of Neuromuscular and
Electrodiagnostic Medicine; American Academy of Physical
Medicine and Rehabilitation. Evidence-based guideline:
Treatment of painful diabetic neuropathy: report of the
American Academy of Neurology, the American Association
of Neuromuscular and Electrodiagnostic Medicine, and the
American Academy of Physical Medicine and Rehabilitation.
Neurology. 2011 May 17;76(20):1758--65.
3. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain:
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4. Kadiroglu AK, Sit D, Kayabasi H, Tuzcu AK, Tasdemir N, Yilmaz
ME. The effect of venlafaxine HCl on painful peripheral diabetic
neuropathy in patients with type 2 diabetes mellitus. J Diabetes
Complications. 2008 Jul-Aug;22(4):241--5.
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release in the treatment of painful diabetic neuropathy: a double-
blind, placebo-controlled study. Pain. 2004 Aug;110(3):697--706.
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