title: Treatment with venlafaxine extended release after SSRI nonresponse or intolerance: a randomized comparison of standard- and higher-dosing strategies.
abstract: OBJECTIVE
  Evaluate efficacy of standard and higher doses of venlafaxine extended release (ER) in depressed outpatients who had either not responded to or could not tolerate an adequate trial of therapy with a selective serotonin reuptake inhibitor (SSRI).
  
  
  METHODS
  Outpatients (n = 232) with major depressive disorder were randomly assigned to 8 weeks of treatment with either "standard" (n = 119; mean dose = 148 mg/d) or "higher" (n = 113; mean dose = 309 mg/d) dosage therapies. Between weeks 8 and 12, nonresponders in the standard dose group could receive higher dose therapy.
  
  
  RESULTS
  Response rates in the higher dose group were significantly greater at week 8 on the Clinical Global Impressions-Improvement scale (68% vs 52%; P < 0.001) and Patient Global Impressions scale (intent-to- treat; 68% vs 52%; P < 0.001). The dosing strategies did not, however, differ significantly in change in HAM-D21 total score or HAM-D21 response or remission rates. At week 12, there were no significant efficacy differences between the two groups in the intent-to-treat sample. Five side effects (constipation, sweating, hypertension, agitation, and urinary frequency) were more common in the high-dose group.
  
  
  CONCLUSIONS
  Higher dose therapy with venlafaxine ER (ie, 300-375 mg/d) resulted in a more rapid response on some measures, but was not as well tolerated as therapy at standard doses. Although these data provide further evidence of a dose-response relationship for venlafaxine therapy results suggest that slower titration to higher doses of venlafaxine ER may improve tolerability without greatly diminishing the probability of success.
authors.affiliation: University of Pittsburgh Medical Center, Department of Psychiatry, Pittsburgh, PA 15213-2593, USA. thaseme@upmc.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.forename: Arifulla
authors.initials: A
authors.lastname: Khan
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride