The SA Journal Diabetes & Vascular Disease Vol 10 No 1 (March 2013) - page 32

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VOLUME 10 NUMBER 1 • MARCH 2013
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
the neuropathic symptom score by one point was thought to be
significant. Ongoing trials are needed to establish whether this
form of treatment might have relevance in treating PDPN.
Modulation of peripheral excitability by blocking excitatory
spinal neuroglia, or increasing spinal inhibition by enhancing
monoaminergic activity is of importance in the processes of neural
sensitisation.
30
Biological approaches include the use of antibodies, siRNA and
gene therapy.
30
Non-pharmacological options
14
Electrical spinal cord stimulation, which is expensive and
invasive.
Transcutaneous electrical nerve stimulation (TENS) has been
used for mild to moderate pain. One class I study reported that
percutaneous electrical nerve stimulation (PENS) reduced pain
in PNDN by 42% on the visual analogue scale compared with
placebo, and also improved sleep. However, a class II study
reported no effect with the treatment.
14
One class III study
showed that the addition of electrotherapy to amitryptiline
was more beneficial than using amitryptiline on its own. It is
recommended as a level B treatment for PNDN.
Magnetic field therapy was not shown to be better than placebo
and should not be used to treat PNDN.
Low-intensity laser therapy (LILT) has not been shown to be any
better than treating with a placebo.
Reiki therapy did not show any benefit in treating PNDN.
Monochromatic near-infrared treatment (MIRE) was not
addressed by the American Academy of Neurology, the
American Association of Neuromuscular and Electro-diagnostic
Medicine, and the American Academy of Physical Medicine and
Rehabilitation.
Opsite dressings showed limited evidence and are not recom-
mended.
Acupuncture, yoga and exercise, e.g. tai chi, are probably no
better than a placebo in treating PNDN, although the use of
acupuncture is perhaps more controversial. Acupuncture was
developed in Chinese medicine in the 5th century BC and
brought to Europe in the 17th century. It is inexpensive, painless,
and the procedure has no side effects. Its efficacy is supported
by a number of small clinical trials. It works by stimulating A-d
and C afferent fibres in muscles, which activate the spinal cord,
midbrain and hypothalamus, leading to release of endorphins
in the peripheral circulation and CSF (cerebrospinal fluid) and
inducing analgesia via encephalins, which block neuropathic
pain.
Treatment options in clinical practice
Taking into account the availability of pharmaceutical agents that
can be used to treat PDPN in South Africa and the cost involved in
treating this condition, bearing in mind that PDPN is not reimbursed
as a prescribed medical benefits condition and that for most patients
the cost of treatment may be a financial burden, the following is a
practical approach to the treatment of PDPN.
The treatment regimen takes into account ADA
31
and NICE
17
guidelines. The recommendations take into account the evidence-
based guidelines advocated by the American Academy of Neurology,
the American Association of Neuromuscular and Electro-diagnostic
Medicine, and the American Academy of Physical Medicine and
Rehabilitation.
Pregabalin represents level A treatment, but is relatively
expensive.
Gabapentin, sodium valproate, venlafaxine, duloxetine, ami-
tryptiline, dextromethorphan, morphine sulphate, tramadol,
oxycodone, capsaicin, isosorbide dinitrate spray and PENS are
all recommended as level B treatment.
Oxcarbazepine, lamotrogine, lacosamide, clonidine, petoxy-
fylline, mexiletene, magnetic field treatment, low-intensity laser
treatment and Reiki therapy are not recommended.
Bearing in mind the cost of pregabalin, either duloxetine, or
amitriptyline should be considered first-line treatment, especially
if there is concomitant depression or a sleep disturbance. The
starting dose of duloxetine is 60 mg/day and the maximum dose
120 mg/day. The starting dose of amitriptyline is 10 mg/day and
the maximum dose 75 mg/day. If there is any drug intolerance,
the duloxetine can be changed to amitriptyline or vice versa. If
affordable, alphalipoic acid 200 mg tid could be added as an anti-
oxidant supplement.
Most cases of PDPN will require multimodal therapy with agents
from two or more classes of drugs. The patient should be carefully
followed up with regular appointments every few weeks, and
re-evaluated by the doctor after six weeks in the clinic. Careful
attention should be given to tight blood sugar control unless
there are clinical reasons to the contrary. It should be stressed
that improvement will not occur unless blood sugar control is
improved. However, too rapid, tight control of the blood sugar may
paradoxically worsen the pain.
If the pain continues and is not relieved by the above regimen,
then either pregabalin 75–150 mg/day in two divided doses or
gabapentin 600 mg tid should be added to either amitriptyline or
duloxetine. If this protocol is ineffective or if the patient’s general
health deteriorates due to severe ongoing pain, or if daily activities
are severely affected by the pain, then referral to a specialist pain
clinic is advisable.
The third line of therapy includes the addition of oral tramadol
200–1 200 mg/day in two or three divided doses, added to either
amitriptyline with or without pregabalin or gabapentin. The use
of tramadol with duloxetine should be used with caution (relative
contraindication) as the combination may result in a serotonergic-
like syndrome. Lidocaine patches can also be used, as can capsaicin
cream, lightly applied to the affected area (the use of capsaicin
for long-term use is not advisable as it may cause unacceptable
irritation of the skin).
The next line of treatment for ongoing pain is the addition
of oxycodone or morphine. A specialist pain centre only should
administer this treatment. If pain is ongoing, it may also be
worthwhile referring the patient for acupuncture.
Conclusion
Painful diabetic peripheral neuropathy is a relatively common
complication of diabetes, occurring most typically in the setting of
older patients with chronic poor glycaemic control and peripheral
vascular disease. The pain may be mild and easily managed
with simple analgesia, a small dose of a tricyclic antidepressant
or an SSNRI drug, or severe and incapacitating, requiring more
complicated drug regimens to control the pain.
It is an important cause of sleep disturbance and poor quality of
life in diabetic patients and the cost of treatment is often a long-
term financial burden when multiple drug-therapy regimens are
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