title: Clinical response to tricyclic antidepressants in functional bowel disorders is not related to dosage.
abstract: BACKGROUND
  As shown in the per protocol analysis of a recent randomized, controlled trial, when tolerated, Desipramine (DES) is effective over placebo (PLA) in treating moderate-to-severe functional bowel disorders (FBD). Clinical experience suggests that the benefit from tricyclic antidepressants (TCA) in FBD can be achieved at doses lower than those used to treat major depression. Within psychiatry, when using higher dosage of TCAs, plasma levels can be used to adjust daily dosage to optimize a treatment response. However, in FBD, it is not known whether plasma levels at the lower dosage are similarly related to a clinical response.
  
  
  OBJECTIVE
  To determine in treating FBD, whether DES blood levels or dose taken can predict a clinical response.
  
  
  METHODS
  As part of a study of 12 wk of antidepressant and psychological treatment in 431 patients with FBD at UNC and U of Toronto, we studied those participants who completed treatment (per protocol analysis) taking DES (N = 97, dose 50-150 mg/day) or pill placebo (PLA) (N = 55 1-3 pills/day). The primary outcome measure was defined as a composite score (Satisfaction with Treatment, McGill Pain Questionnaire, Global Well-being, and IBS-QOL). The composite score was correlated with: (i) DES plasma levels at week 6, and (ii) number of pills taken over the duration of the 12-wk treatment period. In addition, we also compared DES dose with DES plasma levels.
  
  
  RESULTS
  There was a modest correlation between mean DES dose at weeks 5 and 6 and DES blood level at week 6 (R = 0.2 p < 0.07). However, there were no significant correlations between the composite score either with DES dose or with DES blood levels.
  
  
  CONCLUSIONS
  Detectable blood levels of DES are associated with a clinical response in FBD. However, with dosages up to 150 mg, there is no relationship between total dose or plasma level and the clinical response.
authors.affiliation: UNC Center for Functional GI and Motility Disorders, Chapel Hill, North Carolina, USA.
authors.forename: Albena
authors.initials: A
authors.lastname: Halpert
authors.forename: Christine B
authors.initials: CB
authors.lastname: Dalton
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Diamant
authors.forename: Brenda B
authors.initials: BB
authors.lastname: Toner
authors.forename: Yuming
authors.initials: Y
authors.lastname: Hu
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Morris
authors.forename: Shrikant I
authors.initials: SI
authors.lastname: Bangdiwala
authors.forename: William E
authors.initials: WE
authors.lastname: Whitehead
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Drossman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D003109:Colonic Diseases, Functional / Q000188:drug therapy*; D003891:Desipramine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine