Topical analgesics: Topical combination of amitriptyline and ketamine for post herpetic neuralgia

Abstract

The topical application of a combination of a tricyclic antidepressant (A) and an NMDA antagonist (K) was studied for their analgesic efficacy and safety in a neuropathic pain model. 250 subjects with postherpetic neuralgia (PHN) of at least 3 months duration were treated with 4%A/2%K cream for one week in a multicenter enrichment study. 129 subjects(52%)responded and 118 were randomized to either 4%A/2%K (NP-H), 2%A/1%K (NP-L), or placebo (Pl) cream for two additional weeks. At baseline, mean average daily pain intensity (ADP) was 6.5 (0=none to 10=severe). Mean ADP, after three weeks of treatment, was NP-H (3.28), NP-L (4.08), and Pl (4.34) (p=0.026, NP-H vs. Pl). The percentage of subjects who had 30% or greater pain reduction in the randomization phase (last two weeks) was NP-H (46%), NP-L (26%), and Pl (19%) (p=0.025 NP-H vs. Pl). NP-H was superior to placebo for patient global satisfaction (p=0.04) and sleep quality(NP-H 31% vs Pl 17%). Plasma levels of either drug were detected in less than 10% of subjects and those measurable were well below therapeutic levels. The topical cream was well tolerated. This study demonstrated that as an alternative treatment to systemic analgesics, a topically applied combination of a tricyclic antidepressant and an NMDA antagonist to subjects with PHN is effective and safe. The topical application of a combination of a tricyclic antidepressant (A) and an NMDA antagonist (K) was studied for their analgesic efficacy and safety in a neuropathic pain model. 250 subjects with postherpetic neuralgia (PHN) of at least 3 months duration were treated with 4%A/2%K cream for one week in a multicenter enrichment study. 129 subjects(52%)responded and 118 were randomized to either 4%A/2%K (NP-H), 2%A/1%K (NP-L), or placebo (Pl) cream for two additional weeks. At baseline, mean average daily pain intensity (ADP) was 6.5 (0=none to 10=severe). Mean ADP, after three weeks of treatment, was NP-H (3.28), NP-L (4.08), and Pl (4.34) (p=0.026, NP-H vs. Pl). The percentage of subjects who had 30% or greater pain reduction in the randomization phase (last two weeks) was NP-H (46%), NP-L (26%), and Pl (19%) (p=0.025 NP-H vs. Pl). NP-H was superior to placebo for patient global satisfaction (p=0.04) and sleep quality(NP-H 31% vs Pl 17%). Plasma levels of either drug were detected in less than 10% of subjects and those measurable were well below therapeutic levels. The topical cream was well tolerated. This study demonstrated that as an alternative treatment to systemic analgesics, a topically applied combination of a tricyclic antidepressant and an NMDA antagonist to subjects with PHN is effective and safe.