Immediate switching of antidepressant therapy: results from a clinical trial of duloxetine.
BACKGROUND
Approximately half of all treated depressed patients fail to show adequate response to their initially prescribed antidepressant medication. Switching to another medication represents one possible next-step approach for nonresponsive or partially responsive patients. However, specific techniques for switching between antidepressants have not been well studied. We examined the efficacy and tolerability associated with a switch from a selective serotonin reuptake inhibitor (SSRI) or venlafaxine to duloxetine.


METHODS
All patients met criteria for major depressive disorder as defined in DSM-IV. Patients (N = 88) exhibiting suboptimal response or poor tolerability to their current antidepressant medication (citalopram <or=40 mg/d, escitalopram <or=20 mg/d, fluvoxamine <or=150 mg/d, paroxetine <or=40 mg/d, sertraline <or=150 mg/d, or venlafaxine <or=150 mg/d) were switched to duloxetine 60 mg once-daily (QD) without intermediate tapering or titration ("switching" group). A comparator group (N = 67), comprising patients not currently receiving antidepressant medication, initiated duloxetine therapy at 60 mg QD ("initiating" group). Safety assessments included comparisons of discontinuation rates, treatment-emergent adverse events, and changes in vital signs. Efficacy measures included the HAMD(17), Hamilton Anxiety Scale (HAMA), and the Clinical Global Impression of Severity (CGI-S) scale.


RESULTS
The efficacy of duloxetine in switched patients did not differ significantly from that observed in untreated patients initiating duloxetine therapy (mean changes: HAMD(17) total score: -12.3 vs. -12.6; HAMA: -9.36 vs. -9.55, CGI-S: -1.94 vs. -2.12, respectively). However, the rate of discontinuation due to adverse events among patients switched to duloxetine was significantly lower than that in patients initiating duloxetine therapy (4.5% vs. 17.9%, p = .008). Treatment-emergent adverse events occurring in >or=10% of patients in both treatment groups were nausea, headache, dry mouth, insomnia, and diarrhea. Patients switched to duloxetine reported significantly lower rates of nausea and fatigue compared with patients initiating duloxetine.


CONCLUSIONS
In this study, the efficacy of duloxetine in switched patients was comparable to that observed in patients initiating duloxetine therapy. Immediate switching from an SSRI or venlafaxine to duloxetine (60 mg QD) was well tolerated.
Wohlreich
Madelaine M
MM
Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285, USA. mwmd@lilly.com
Mallinckrodt
Craig H
CH
Watkin
John G
JG
Wilson
Michael G
MG
Greist
John H
JH
Delgado
Pedro L
PL
Fava
Maurizio
M
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects; D015283:Citalopram / Q000009:adverse effects; D003511:Cyclohexanols / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000009:adverse effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects; D013876:Thiophenes / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D015283:Citalopram; D003511:Cyclohexanols; D000068736:Duloxetine Hydrochloride; D016666:Fluvoxamine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D013876:Thiophenes; D000069470:Venlafaxine Hydrochloride