Neuropathic Pain Pilot Study: AMI and KET

[Guest guest]

The Clinical Journal of Pain 2003; 19(5):323-328

A Pilot Study Examining Topical Amitriptyline, Ketamine, and a

Combination of Both in the Treatment of Neuropathic Pain

*M. E. Lynch, MD, FRCPC; †A. J. , MD, FRCPC; ‡J. Sawynok, PhD

Abstract:

Objective:

The involvement of ongoing peripheral activity in the generation of

nociceptive input in neuropathic pain suggests that topical drug

delivery may be useful as a treatment strategy. This is a pilot study

providing initial information regarding the use of novel topical

preparations containing amitriptyline (AMI), ketamine (KET), and a

combination of both in the treatment of neuropathic pain.

Methods:

The study design included a 2 day randomized, double blind, placebo

controlled, 4 way cross-over trial of all treatments, followed by an

open label treatment phase using the combination cream for 7 days.

Twenty volunteers with chronic neuropathic pain were randomly assigned

to treatment order and applied 5 mls of each topical treatment (1% AMI,

0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures

of pain at the end of each block included the short form McGill Pain

Questionnaire (MPQ) and visual analog scales (VAS) for present pain

intensity and pain relief. Eleven subjects who judged subjective

improvement from any treatment in the initial trial entered the

open-label trial and used the combination cream for 7 days. Pain levels

were recorded daily using the same measures. Blood levels for

amitriptyline and ketamine were performed at 7 days to determine whether

systemic absorption had occurred.

Results:

There was no statistically significant difference from placebo after 2

days for any treatment during the double blind component of the trial.

In the 11 subjects who used the combination cream, there was a

statistically significant effect, with subjects reporting significantly

greater analgesia by days 3 to 7 according to measures of pain and pain

relief. Blood levels revealed that there was no significant systemic

absorption of amitriptyline or ketamine. Only 2 subjects experienced

side effects; these were minor and did not lead to discontinuation of

the cream.

Conclusion:

This pilot study demonstrated a lack of effect for all treatments in the

2 day double blind placebo controlled trial, followed by analgesia in an

open label trial in a subgroup of subjects who chose to use the

combination cream for 7 days. Blood analysis revealed no significant

systemic absorption of either agent after 7 days of treatment, and

creams were well tolerated. A larger scale randomized trial over a

longer interval is warranted to examine further effects observed in the

open label trial.

Pain Management Unit, Queen II Health Sciences Centre,

*Department of Psychiatry and †Anesthesia, Dalhousie University,

Halifax, Nova Scotia; and ‡Department of Pharmacology, Dalhousie

University, Halifax, Nova Scotia

Corresponding author: Lynch, MD, FRCPC, Director of Research, Pain

Management Unit, Queen II Health Sciences Centre, 4th Floor

Dickson Centre, Room 4086, Halifax, Nova Scotia, B3H 1V7.