SA JOURNAL OF DIABETES & VASCULAR DISEASE
CURRENT TOPICS
VOLUME 7 NUMBER 4 • NOVEMBER 2010
141
prescribing them mainly as an add-on to other therapy, there is little
clinical evidence to support this approach. In one cross-over study,
low-dose combination therapy with gabapentin and morphine was
significantly more effective than either treatment alone at a higher
dose.
27
Unfortunately, combination treatment was associated with
a higher frequency of adverse effects than monotherapy.
27
Recently,
prolonged-release oxycodone was also found to enhance the effects
of existing gabapentin therapy in patients with painful DPN.
28
Other agents
Several other drugs including: (1) the peripheral nerve terminal
substance P depleter, topical capsaicin (0.075%) applied sparingly
three or four times per day to the affected area.
29
and (2) the
antioxidant,
a
-lipoic acid (600 mg/day intravenously or orally)
30,31
have also been also been found to relieve neuropathic pain.
Finnerup NB,
et al
. showed that the NNTs for the various drugs in
painful neuropathy that have undergone clinical trials.
32
The size of
circles reflects the total number of patients involved in trials. TCAs
have the lowest NNTs.
16,32
However, most were small studies, and
some were cross-over trials which is likely to lower the NNT.
16
Thus
caution needs to be exercised in interpreting these; indeed with
some of the trials it is like comparing apples and oranges due to the
variation in trial design and endpoints.
TCAs also have increased risk of adverse side effects,
including sedation, dry mouth, sweating, dizziness, as well as
contraindications for use in heart disease, epilepsy and glaucoma.
16
The largest number of patients in trials involved pregabalin,
duloxetine, and gabapentin, and these compounds appear to
have similar intermediate efficacy. Nausea is more common with
duloxetine
19-21
while dizziness and somnolence are more common
with pregabalin and gabapentin.
23,24
NICE guidance treatment algorithm (Fig. 1)
The recent NICE guideline in the management of type 2 diabetes
33
advocates a ‘formal enquiry annually’ about the development
of neuropathic symptoms that may be causing distress. It also
encourages clinicians to be alert to the psychological consequences
of painful DPN and the need to offer psychological support
according to the needs of the individual.
The guideline recommends the use of a TCA as first-line agent
principally because they are cheaper compared to the second-line
agents. Unfortunately, there have been no large, head-to-head
comparisons between TCAs, duloxetine and pregabalin/gabapentin,
and in the absence of this it is impossible to know which drug
is the most efficatious. The NICE guideline then recommends the
use of duloxetine, gabapentin or pregabalin if a trial of TCA has
not provided effective pain relief. The choice of a second-line drug
would be determined by drug prices. Finally, NICE suggests the use
of opiate analgesia if severe chronic pain persists despite trials of
other measures. If there is inadequate relief of the pain despite
Figure 1.
Neuropathic pain management. Reproduced with permission.
33
1
Tricyclic drugs can increase the likelihood of side effects such as orthostatic hypotension in a person with autonomic neuropathy
2
When neurological symptoms are not adequately controlled, it may be helpful to discuss:
• reasons for the problem
• likelihood of remission in the medium term
• role of improved blood glucose control
Reproduced with permission from National Institute for Health and Clinical Excellence (NICE) (2009)
CG 87 Type 2 diabetes: the management of type 2 diabetes
.
London: NICE. Available from
33
Every year, formally ask about neuropathic sysptoms
If present:
• discuss cause and prognosis
• agree appropriate therapeutic options and review understanding at
each clinical contact
• be alert to psychological consequences and offer support appropriate
to need
Offer tricyclic drug, starting at low doses; titrate as tolerated
1
Discuss timing for most benefit
Advise that it is a trial of therapy
Offer trial of cheapest (at maximum dose) of duloxetine, gapentin or
pregabalin
Stop if ineffective at maximally tolerated dose
Try another of the drugs if side effects limit dose titration
Consider trial of opiate analgesia
Discuss with the person and seek assistance of local chronic pain
management team if agreeable
Uncontrolled
Uncontrolled
Uncontrolled
2
Uncontrolled
Controlled
Consider reducing dosage/stopping therapy following
discussion and agreement with person concerned
