Topical Ketamine For Post-herpetic Neuralgia

I’m trying to complete my coverage of Post-herpetic Neuralgia (PHN) treatments and felt this was a rather newer innovation. 65% can achieve a significant reduction in pain.

Ketamine has been used by itself for PHN:
Topical ketamine treatment of postherpetic neuralgia
Quan et al.
Neurology.2003; 60: 1391-1392  abstract here

Their ketamine preparation was rather involved:

“Ketamine preparation. Soybean lecithin granules 250 g; Spectrum LE 102) were mixed with 150 mL isopropyl palmitate (Aldrich Chemical #29–178–1, Milwaukee, WI). The mixture was stirred at least 12 hours until a uniformly dark, amber-colored solution was obtained. Ketamine (10 mL; Ketalar N0071–4582–10, 50 mg/mL) was added to a final concentration of 5 mg ketamine/mL gel.” – This should be 0.5% ketamine

I have found ketamine in PLO gels just too irritating to use but can be used in Lipoderm.

• PHN patients treated with topical ketamine alone or in addition to a stable pre-existing medication: – 16 cases
  – 5 reported a reduction in pain from severe to moderate
  – 5 reported a reduction from severe to mild.

On average dropped pain from 7 t0 5.5 –  (down 1.5/10) which is not great by self but ok if you start amitriptyline or lyrica etc. at same time…

Another study used ketamine at double the strength -1% and found adding amitriptyline 2% did not make a difference:
Anesthesiology: July 2005 – Volume 103 – Issue 1 – pp 140-146
Topical 2% Amitriptyline and 1% Ketamine in Neuropathic Pain Syndromes: A Randomized, Double-blind, Placebo-controlled Trial
Lynch, Mary E. M.D., F.R.C.P.C.*; Clark, Alexander J. M.D., F.R.C.P.C.†; Sawynok, Jana Ph.D.‡; Sullivan, Michael J. L. Ph.D.  free article here

Another study used Ketamine at 2%, and added amitriptyline and felt they got even better results:

APS meeting Vancouver 2007 Poster #: 787
Title: A multicenter, double-blind, randomized, placebo controlled study of the efficacy/safety of two doses of amitriptyline/ketamine topical cream in treating post-herpetic neuralgia (PHN)
Authors: D Everton, D Bhagwat,M Damask;  ref here

reating chronic pain is a challenge (severe side-effects of systemic drugs). When efficacious, topically delivered drugs are excellent alternatives. This study was conducted to evaluate the efficacy and safety of amitriptyline 4%/ketamine 2% [NP-H] and amitriptyline 2% /ketamine1% [NP-L] topical creams versus placebo in 251 PHN patients. Patients applied the NP-H twice daily for one week. Of this group, 129 subjects met the entry criteria for randomization (> one point decrease in average daily pain (ADPS) for 3 of the seven days). In this group, the ADPS (NRS 0-10) changed from 6.5 + 1.7 at baseline to 3.8 + 1.8 at the end of one week (p< 0.0001), a decrease of 42%. Of these, 118 were entered into the second phase in which the patients were randomized to placebo, NP-H, or NP-L cream applied b.i.d. for 14 days. Although the placebo subjects did not return to baseline, (4.5 + 2.0 to 4.4 + 2.2), the NP-H group, had an additional decrease in ADPS from day 8 to day 21 from 4.4 + 2.1 to 3.3 + 2.1. The difference between NP-H and placebo at day 21 was statistically significant (p=0.03). The primary analysis, change in daily average pain intensity from baseline (day 1) to day 21, was also statistically significant between NP-H and placebo (p=0.026). A responder analysis (>30% decrease in ADPS between day 8 and day 21) demonstrated that NP-H was superior to placebo (46% versus 19%, p<0.025) Patient global satisfaction and was significantly better for NP-H versus placebo (p=0.04). NP-H was superior to placebo for change in sleep quality from baseline to day 21 (p=0.028). NP-H was numerically superior to NP-L cream and appears to be the optimal concentration for PHN treatment. Less than 5% of subjects who applied NP-H had detectable levels of amitriptyline or ketamine

This study got pain from 6.5 to 3.8/10 (down 2.7) which is actually a more meaningful drop

Addendum:

Recent study added 5% lidocaine as well in a gel:
1. Support Care Cancer. 2011 Aug 17. [Epub ahead of print]
Topical amitriptyline, ketamine, and lidocaine in neuropathic pain caused by radiation skin reaction: a pilot study.
Uzaraga I, Gerbis B, Holwerda E, Gillis D, Wai E.

• amitriptyline 2%, ketamine 1% and lidocaine 5%
• dropped pain by 2.9/10

Comment – ketamine topically becomes an adjunct but going to need other agents. Looks to me that Amitriptyline 4%,  Ketamine 2%, and lidocaine 5%  in Lipoderm might be the best combo. Adding 1% hydrocortisone cream might be useful in easily irritated cases.