Therapeutic efficacy and safety of amitriptyline in patients with cystic fibrosis.
Amitriptyline, a blocker of acid sphingomyelinase and acid ceramidase, significantly reduces Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) mice with concurrent increase of survival. Our aim was to establish whether amitriptyline is safe and effective in the treatment of CF patients. In a randomised, double-blinded, placebo-controlled, cross-over pilot study, 4 adult CF patients received 37.5 mg of amitriptyline or placebo twice daily for 14 days. Subsequently in a phase II study 19 adult CF patients were randomly allocated to three treatment groups receiving amitriptyline once daily for 28 days at doses of 25 mg (n=7), 50 mg (n=8), or 75 mg (n=8) or placebo (n=13). The primary outcome was the difference of forced expiratory volume in 1 sec (FEV(1)) at day 14 between amitriptyline and placebo. Primary endpoint measures improved significantly in three of four patients in the pilot study after amitriptyline treatment vs placebo (relative FEV(1): 14.7+/-5%; p = 0.006) and in the 25 mg treatment group of the phase II study (relative FEV(1): 4.0+/-7%; p = 0.048). Amitriptyline was well tolerated in both studies and 96% of the patients completed the studies. Amitriptyline as a novel therapeutic option in patients with CF is safe and seems to be efficacious.
Riethmüller
Joachim
J
Department of Paediatrics, University Hospital Tuebingen, Tuebingen, Germany. joachim.riethmueller@med.uni-tuebingen.de
Anthonysamy
Janina
J
Serra
Emilio
E
Schwab
Matthias
M
Döring
Gerd
G
Gulbins
Erich
E
D000328:Adult; D000639:Amitriptyline / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D000639:Amitriptyline