title: Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline.
abstract: OBJECTIVE
  Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF). Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a benefit in lung function, weight and exacerbation rates.
  
  
  METHODS
  To test for a beneficial effect of amitriptyline in vivo, we performed two phase II randomised, double-blind, placebo-controlled studies. CF patients were treated with 25 mg amitriptyline twice daily, i.e. a total dose of 50 mg/d. After those two studies part of the patients used amitriptyline in an off-lable-use for routine treatment. These patients were observed after one, two and three years after continuous use of amitriptyline and were matched with those patients who were not treated. These patients were used as a control group.
  
  
  RESULTS
  After one year of treatment, forced expiratory volume in 1 sec predicted (FEV1) increased significantly by 7.6±7.0%, p=<0.001, and weight increased by 2.1±2.3kg, p=<0.001 in the amitriptyline population (n=20), whereas FEV1 decreased significantly in the control group by 1.8±3.3%, p=0.010, and weight increased by 1.1±2.7kg, p=0.010 (n=14). After two years of treatment, FEV1 increased significantly by 5.6±10.3%, p=0.009, and weight increased by 3.6±2.9kg, p=<0.001 in the amitriptyline population (n=12). In contrast, FEV1 decreased in the control group by 2.1±3.7%, p=0.051 and weight increased by only 0.4±2.9kg, p=0.31 (n=10). After three years of treatment, FEV1 increased significantly by 7.7±8%, p=0.050, and weight increased by 7.3±3.8kg, p=0.016, in the amitriptyline population (n=5), whereas FEV1 decreased in the control group by 1.0±1.3%, p=0.075 and weight increased by 0.4±1.5kg, p=0.29 (n=5).
  
  
  CONCLUSIONS
  Amitriptyline significantly increases FEV1, reduces ceramide in lung cells and increases weight of CF patients.
authors.affiliation: Department of Paediatrics, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Adams
authors.forename: Vanya
authors.initials: V
authors.lastname: Icheva
authors.forename: Caroline
authors.initials: C
authors.lastname: Deppisch
authors.forename: Josefine
authors.initials: J
authors.lastname: Lauer
authors.forename: Gloria
authors.initials: G
authors.lastname: Herrmann
authors.forename: Ute
authors.initials: U
authors.lastname: Graepler-Mainka
authors.forename: Susanne
authors.initials: S
authors.lastname: Heyder
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.forename: Joachim
authors.initials: J
authors.lastname: Riethmueller
mesh_terms: D000328:Adult; D000639:Amitriptyline / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism*; D017322:Clinical Trials, Phase II as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D015337:Multicenter Studies as Topic; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002518:Ceramides; D000639:Amitriptyline