Duloxetine in the treatment of major depressive disorder: an open-label study.
BACKGROUND
Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.


METHODS
Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17) total score >or=18 and a Clinical Global Impression of Severity (CGI-S) score >or=4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.


RESULTS
The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by >or=10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.


CONCLUSIONS
In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.
Hudson
James I
JI
McLean Hospital, Belmont, MA, USA. jhudson@mclean.harvard.edu
Perahia
David G
DG
Gilaberte
Inmaculada
I
Wang
Fujun
F
Watkin
John G
JG
Detke
Michael J
MJ
D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004185:Disability Evaluation; D000068736:Duloxetine Hydrochloride; D006801:Humans; D011788:Quality of Life / Q000523:psychology; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D011795:Surveys and Questionnaires; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes