Dose-response relationship of duloxetine in placebo-controlled clinical trials in patients with major depressive disorder.
BACKGROUND
The optimal dose for achieving the maximum antidepressive effect of selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenalin reuptake inhibitors (SNRIs) remains a controversial issue. The varying sensitivity of scales that measure the severity of depression is one of the many factors affecting the evaluation of the dose-response relationship with antidepressants.


OBJECTIVE
To determine if the 6-item Hamilton rating scale for depression (HAM-D6) demonstrates a clearer association between dose and antidepressive effect compared with the 17-item Hamilton rating scale for depression (HAM-D17) for fixed doses of duloxetine hydrochloride (40, 60, 80, and 120 mg daily) from six double-blind, randomized, placebo-controlled clinical trials assessing safety and efficacy in the acute treatment of patients with DSM-IV-defined major depressive disorder (MDD).


METHODS
Mantel-Haenszel adjusted effect sizes were determined by dose for change from baseline to endpoint in HAM-D6 and HAM-D17 scores from the six studies. To confirm, assessments were repeated on the subset of the population corresponding to the 70% of patients with the longest duration of treatment regardless of study, treatment, dose, geography, or completion status.


RESULTS
For the majority of assessments, HAM-D6 effect sizes were numerically larger than those estimated from the HAM-D17. Findings support that duloxetine 60 mg daily is the best effective dose.


CONCLUSIONS
In this assessment of patients with MDD, the HAM-D6 was shown to be more sensitive compared with the HAM-D17 at detecting treatment effects. These findings are consistent with published results of other effective antidepressants.
Bech
Per
P
Psychiatric Research Unit, Frederiksborg General Hospital, Dyrehavevej 48, DK-3400, Hilleroed, Denmark. pebe@fa.dk
Kajdasz
Daniel K
DK
Porsdal
Vibeke
V
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000328:Adult; D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068736:Duloxetine Hydrochloride; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D013876:Thiophenes / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes