title: Pulse-loaded intravenous clomipramine in treatment-resistant obsessive-compulsive disorder.
abstract: BACKGROUND
  Small studies have suggested that intravenous clomipramine (CMI) may be more effective and induce faster improvement in obsessive-compulsive disorder than do orally administered serotonin reuptake inhibitors.
  
  
  OBJECTIVE
  To test these hypotheses, we conducted a randomized, double-blind, double-dummy study of pulse-loaded intravenous versus oral CMI, followed by open-label oral CMI for 12 weeks.
  
  
  METHODS
  We enrolled a volunteer and referred group of 34 adults with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition obsessive-compulsive disorder of > or =1-year duration and Yale-Brown Obsessive Scale score of > or =20. Eligible subjects had failed > or =2 adequate serotonin reuptake inhibitor trials. Subjects received pulse loaded CMI 150 mg by vein or by mouth on day 1 and 200 mg on day 2. Oral CMI began on day 6 at 200 mg/d and was increased by 25 mg every 4 days to 250 mg/d, as tolerated, for 12 weeks.
  
  
  RESULTS
  Adverse events led to one withdrawal during oral pulse loading and 5 during open-label oral treatment. Intravenous pulse loading did not induce a more rapid or greater Yale-Brown Obsessive Scale score decrease than oral pulse loading at day 6 or by week 12. Day 6 and week 12 improvement were unrelated to plasma drug or metabolite concentrations. Pulse loading itself seemed to induce more rapid and greater improvement than expected in treatment-resistant obsessive-compulsive disorder.
  
  
  CONCLUSIONS
  Further investigation of oral pulse-loading regimens in treatment-resistant obsessive-compulsive disorder is warranted.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA. lkoran@stanford.edu
authors.forename: Lorrin M
authors.initials: LM
authors.lastname: Koran
authors.forename: Elias
authors.initials: E
authors.lastname: Aboujaoude
authors.forename: Herbert
authors.initials: H
authors.lastname: Ward
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Shapira
authors.forename: Floyd R
authors.initials: FR
authors.lastname: Sallee
authors.forename: Nona
authors.initials: N
authors.lastname: Gamel
authors.forename: Michael
authors.initials: M
authors.lastname: Elliott
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002997:Clomipramine / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D002997:Clomipramine; D017367:Selective Serotonin Reuptake Inhibitors