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Neuropathy – diabetic 281
confirms the utility of once-daily HS doses of TCAs such as amitriptyline (75
mg) or imipramine (titrated up to 150 mg). 6,7
Multiple RCTs have demonstrated the efficacy of the serotonin–
norepinephrine reuptake inhibitor (SNRI) duloxetine in the treatment of
DN. 8–11 The initial dose of duloxetine forDNis60mgQD;iftheinitialQD
dose is well tolerated but insufficient at controlling pain, 60 mg may be taken
BID (some authorities use a single HS dose of 120 mg). In elderly patients, or
those with renal impairment, or any patient for whom tolerability may be a
concern, a starting dose of 20 mg QD may be slowly advanced to 40–60 mg
daily (administered in either one or two doses). The SNRI venlafexine is also
effective for DN, with a dose in the range 75–225 mg QD. With the SNRIs, pain
relief may occur as early as one to two weeks after institution of therapy,
though some patients may not see a full effect for up to six weeks. A withdrawal
syndrome can occur if the SNRIs are abruptly discontinued.
Anticonvulsants are a valuable therapeutic option in DN. Gabapentin’s
utility is demonstrated consistently in multiple RCTs; significant pain relief
is found in approximately one in four patients. 12–14 The PO dosing of gabapentin
for DN follows an advancing regimen: 300 mg HS on day one, followed
by 300 mg BID on day two, then 300 mg TID on day three. The drug
can then be titrated up to 1800 mg/day over two weeks.
Pregabalin (in a daily dose of 300–600 mg, administered in two or three
divided doses) is effective for DN as well; approximately five patients must be
treated for pain relief to be achieved in one. 15–17 When used in neuropathic
pain, pregabalin achieves pain reduction by the end of therapy’s first week;
maximal analgesia is reached within four weeks. 18
Topical application of local anesthetics may be useful in patients with
focal DN pain. Patch application of lidocaine (5% preparation, applied for up
to 4 h alternating with 12 h off), is known to be effective in DN; about one in
four patients will respond. 19,20
Intravenously injected local anesthetics have been reported potentially useful
in DN. For example, bolus doses of lidocaine (a 5 mg/kg dose) are reported
to achieve DN pain relief for up to three weeks post-injection. 21 However,
lidocaine injection’s overall risk-to-benefit ratio is not as favorable as those of
other therapies, so there is little role for bolus lidocaine in ED treatment of DN.