title: Phase Ia and Ib study of amitriptyline for ulnar nerve block in humans: side effects and efficacy.
abstract: BACKGROUND
  The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain conditions. Among its many actions, this drug also blocks ion channels, such as Na channels. Preliminary animal studies suggested that amitripty-line would be a longer-lasting local anesthetic than bupivacaine, with potentially fewer side effects. Therefore, the authors investigated the adverse effects and effectiveness of this drug when given for ulnar nerve blockade in human volunteers.
  
  
  METHODS
  After obtaining written institutional review board approval and informed consent, a typical phase Ia trial was conducted by administration to the ulnar nerve at the level of the wrist in an open-label, dose-escalating fashion. Amitripty-line hydrochloride, 4 ml, at concentrations of 5, 10, and 20 mM (n = 4-9/group) was used for each volunteer. If no major side effects and nerve block were encountered, comparison in a randomized, double-blinded trial of amitriptyline (20 mM) to placebo and bupivacaine (4 mM) (n = 4-9/group), was to follow. A blunt needle was used to grade the pain, and motor blockade was assessed by the Froment test.
  
  
  RESULTS
  There was no significant statistical difference in terms of side effects (pain, swelling, erythema, and sedation) among any groups. The analgesic effects of 20 mM amitriptyline and 4 mm bupivacaine solution were significantly higher than those of the placebo solution.
  
  
  CONCLUSIONS
  Because of the lack of evidence that amitripty-line provides better nerve blockade than current local anesthetics and the potential for neurotoxicity, its use for peripheral nerve blockade in humans seems limited.
authors.affiliation: Trauma Hospital Lorenz Boehler, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Fridrich
authors.forename: Sunil
authors.initials: S
authors.lastname: Eappen
authors.forename: Walter
authors.initials: W
authors.lastname: Jaeger
authors.forename: Eva
authors.initials: E
authors.lastname: Schernhammer
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Zizza
authors.forename: Ging Kuo
authors.initials: GK
authors.lastname: Wang
authors.forename: Peter
authors.initials: P
authors.lastname: Gerner
mesh_terms: D000328:Adult; D000639:Amitriptyline / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D002045:Bupivacaine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D004311:Double-Blind Method; D004890:Erythema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009407:Nerve Block / Q000379:methods*; D010146:Pain / Q000139:chemically induced; D014459:Ulnar Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D000639:Amitriptyline; D002045:Bupivacaine