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294 Neuropathy – overview
Gabapentin and pregabalin are the main newer-generation anticonvul-
sants with utility in NP. These agents work by inhibiting calcium channels
and the release of neurotransmitters (e.g. substance P).
Gabapentin’s effectiveness in a variety of types of NP is shown in multiple
RCTs. 20–22 High potential for broad clinical application of gabapentin for NP
is indicated by numerous human and animal NP studies delineating the
drug’s utility (and its superiority over other anticonvulsants). The usual
dose of gabapentin for NP is 600–1200 mg PO TID; for patients with resistant
NP, optimal pain relief is achieved with a combination approach of an opioid
and gabapentin. 23
Pregabalin is similar to gabapentin in both mechanism of action and
breadth of potential application in NP. 24–26 Pregabalin is reported to be
useful in some types of NP (e.g. after spinal cord injury) that are historically
refractory to pharmacotherapy. 26 The daily dose of pregabalin for NP starts at
150 mg PO (typical dosage range is 50–100 mg PO TID).
When used for NP, gabapentin and pregabalin are expected to decrease
pain scores by at least 50% after one week of therapy; some effect is seen even
earlier. 24
The pain relief efficacy of the newer-generation anticonvulsants is complemented
by the fact that, compared with many therapeutic alternatives in
NP, gabapentin and pregabalin are safer. The newer agents have lesser
toxicity and fewer side effects. Drug interactions are less of a risk, and
ongoing hepatic or hematologic monitoring is unnecessary. Both gabapentin
and pregabalin undergo renal metabolism, necessitating dosage adjustment
in patients with renal failure. Pregabalin does offer a few advantages over
gabapentin. It has faster onset, and starting doses are more likely to be
clinically effective. Pregabalin can also be rapidly titrated upward in patients
needing more pain relief. Neither drug should be stopped abruptly, but
instead should be tapered over at least one week to prevent withdrawal
symptoms.
There is also evidence addressing use of another new-generation anticonvulsant,
lamotrigine, for NP. A 2007 Cochrane review of available data found
no role for lamotrigine for the general patient population with NP, or for any
NP subgroups. 27