title: [Dose-escalation of SSRIS in major depressive disorder. Should not be recommended in current guidelines].
abstract: BACKGROUND
  In cases where patients with unipolar depression do not respond to a standard dose of selective serotonin reuptake inhibitors (SSRIS), treatment guidelines often recommend a higher dose. A systematic review of the literature revealed uncertainty about the efficacy of dose escalation and pointed to methodological weaknesses in earlier research.
  
  
  OBJECTIVE
  To review current practice and results concerning dose-escalation of SSRIS.
  
  
  METHODS
  We made a summary of previously published English articles that systematically reviewed previous SSRI-dose-escalation studies in depressed patients and present the results of a recent double-blind randomised dose-escalation study of paroxetine. By means of a 123I-β-cit-spect study in a subgroup of the patients in the recent dose-escalation study it was possible to measure the amount of paroxetine bound to serotonin transporters. This provided combined clinical and pharmacological outcomes.
  
  
  RESULTS
  The study with paroxetine provided clinical evidence that dose-escalation of paroxetine in depression was not effective and that adverse effects increased. The occupancy of the serotonin-transporters did not increase significantly after dose-escalation, despite increases in paroxetine serum levels.
  
  
  CONCLUSIONS
  Dose-escalation of ssris for patients with unipolar depression who did not respond to a standard dose, does not improve response or the chance of remission. The pharmacological explanation for this is that the occupancy of the serotonin-transporters does not increase following dose-escalation.
authors.affiliation: Universiteit van Amsterdam, Amsterdam. H.G.Ruthe@amc.uva.nl
authors.forename: H G
authors.initials: HG
authors.lastname: Ruhé
authors.forename: J
authors.initials: J
authors.lastname: Booij
authors.forename: H C
authors.initials: HC
authors.lastname: van Weert
authors.forename: J B
authors.initials: JB
authors.lastname: Reitsma
authors.forename: E J
authors.initials: EJ
authors.lastname: Franssen
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
authors.forename: A
authors.initials: A
authors.lastname: Schene
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors