Incidence and duration of antidepressant-induced nausea: duloxetine compared with paroxetine and fluoxetine.
OBJECTIVE
This analysis assessed the incidence, severity, onset, and duration of nausea among patients with major depressive disorder (MDD) treated with the new antidepressant duloxetine.


METHODS
Data were pooled from 8 double-blind, randomized, placebo- and active comparator-controlled trials employing patients with MDD that were submitted to the US Food and Drug Administration to support duloxetine's new drug application for treatment of MDD.


RESULTS
The numbers of patients receiving each regimen were as follows: placebo, n = 777; duloxetine 40 mg/d, n = 177; duloxetine 60 mg/d, n = 251; duloxetine 80 mg/d, n = 363; duloxetine 120 mg/d, n = 348; paroxetine 20 mg/d, n = 359; and fluoxetine 20 mg/d, n = 70. In acute placebo-controlled trials of duloxetine 40 to 120 mg/d, treatment-emergent nausea was reported by more duloxetine-treated patients than those receiving placebo (19.9% [227/1139] vs 6.9% [154/777], respectively; P <0.001). Among duloxetine-treated patients, the median time to onset of nausea was 1 day, and the median duration of nausea was 7 days. The incidence of nausea was similar to placebo rates after 1 week. In paroxetine-controlled studies, the incidence of treatment-emergent nausea in patients receiving duloxetine did not differ significantly from paroxetine (14.4% vs 12.0%, respectively). In head-to-head studies, the incidence of treatment-emergent nausea with duloxetine did not differ significantly from that with fluoxetine (17.1% vs 15.7%, respectively). Most duloxetine-treated patients reported nausea to be mild (52.9%) or moderate (41.4%). Treatment discontinuation secondary to nausea occurred in more duloxetine-treated patients than those receiving placebo (1.4% [16/1139] vs 0.1% [1/777], respectively; P = 0.002). Following abrupt discontinuation after acute treatment, 5.9% of duloxetine-treated patients exhibited nausea compared with 0.3% of patients receiving placebo (P < 0.001). The incidence of treatment-emergent nausea during 6-month continuation of duloxetine treatment (80 mg/d, 2.1%; 120 mg/d, 1.3%) was similar to placebo (1.6%). Following abrupt discontinuation after 8 months of treatment, nausea was reported by 1.6% of patients receiving duloxetine 120 mg/d compared with 0% for those receiving duloxetine 80 mg/d and 0% for placebo.


CONCLUSIONS
Duloxetine induced mild to moderate nausea in a subset of patients with MDD during treatment initiation. Nausea resolved rapidly with continued treatment. The incidence of duloxetine-induced nausea resembled that produced by paroxetine and fluoxetine.
Greist
John
J
Healthcare Technology Systems, Madison, Wisconsin 53717, USA. jgreist@healthtechsys.com
McNamara
Robert K
RK
Mallinckrodt
Craig H
CH
Rayamajhi
Jyoti N
JN
Raskin
Joel
J
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D005060:Europe / Q000453:epidemiology; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced* / Q000453:epidemiology; D017374:Paroxetine / Q000009:adverse effects* / Q000627:therapeutic use; D015995:Prevalence; D012720:Severity of Illness Index; D012737:Sex Factors; D013876:Thiophenes / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D013876:Thiophenes; D005473:Fluoxetine; D017374:Paroxetine; D000068736:Duloxetine Hydrochloride