Profile of adverse events with duloxetine treatment: a pooled analysis of placebo-controlled studies.
BACKGROUND
The serotonin and noradrenaline (norepinephrine) reuptake inhibitor duloxetine has been approved in the US and elsewhere for a number of indications, including psychiatric illnesses and chronic pain conditions. Because the patient populations are diverse within these approved indications, and duloxetine is not yet approved for treatment of other conditions, we wanted to determine if adverse event profiles would differ among patients being treated for these various conditions.


OBJECTIVE
To provide detailed information on the adverse events associated with duloxetine and to identify differences in the adverse event profile between treatment indications and patient demographic subgroups.


METHODS
Data were analysed from all placebo-controlled trials of duloxetine completed as of December 2008. The 52 studies included 17,822 patients (duloxetine n = 10,326; placebo n = 7496) with major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, osteoarthritis knee pain (OAKP), chronic lower back pain and lower urinary tract disorders. The main outcome measures were rates of treatment-emergent adverse events (TEAEs) and adverse events reported as the reason for discontinuation.


RESULTS
The overall TEAE rate was 57.2% for placebo-treated patients and 72.4% for duloxetine-treated patients (p < or = 0.001). Patients with OAKP had the lowest TEAE rate (placebo 36.7% vs duloxetine 50.2%, p < or = 0.01), while patients with fibromyalgia had the highest rate (placebo 80.0% vs duloxetine 89.0%, p < or = 0.001). The most common TEAE for all indications was nausea (placebo 7.2% vs duloxetine 23.4%, p < or = 0.001), which was predominantly mild to moderate in severity. No statistically significant treatment-by-subgroup interactions for age were found between placebo and duloxetine treatment for the most common TEAEs. The rates of duloxetine-associated dry mouth and fatigue were greater in women than in men (13.1% vs 10.4%, interaction p = 0.004; and 9.4% vs 7.6%, interaction p = 0.03, respectively). Duloxetine-associated dry mouth incidence was higher in Caucasians than non-Caucasians (13.2%, 11.0%, interaction p = 0.04).


CONCLUSIONS
Duloxetine treatment is associated with significantly higher rates of common TEAEs versus placebo, regardless of indication or demographic subgroup. Differences across indications are likely to be attributable to the underlying condition rather than duloxetine, as suggested by the similar trends observed in placebo- and duloxetine-treated patients.
Brunton
Stephen
S
Faculty Development, Cabarrus Family Medicine Residency, Concord, North Carolina, USA.
Wang
Fujun
F
Edwards
S Beth
SB
Crucitti
Antonio S
AS
Ossanna
Melissa J
MJ
Walker
Daniel J
DJ
Robinson
Michael J
MJ
D000367:Age Factors; D000928:Antidepressive Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D044469:Racial Groups; D016032:Randomized Controlled Trials as Topic; D012737:Sex Factors; D013876:Thiophenes / Q000009:adverse effects*
D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride
Pain. 1999 Dec;83(3):389-400
10568846
Prog Neurobiol. 2002 Apr;66(6):355-474
12034378
Pain Med. 2005 Sep-Oct;6(5):346-56
16266355
Eur J Neurol. 2009 Sep;16(9):1041-8
19469829
J Clin Psychiatry. 2007 Nov;68(11):1707-16
18052564
Neurourol Urodyn. 2008;27(3):212-21
17580357
Int Urogynecol J Pelvic Floor Dysfunct. 2005 Sep-Oct;16(5):337-44
15662490
J Clin Psychiatry. 2006 Sep;67(9):1379-90
17017824
Prog Brain Res. 1991;88:381-94
1813927
J Clin Psychiatry. 2007 Dec;68(12):1921-30
18162024
Eur Neuropsychopharmacol. 2004 Dec;14(6):457-70
15589385
Arthritis Rheum. 2004 Sep;50(9):2974-84
15457467
Eur Psychiatry. 2006 Sep;21(6):367-78
16697153
BJU Int. 2004 Feb;93(3):311-8
14764128
J Affect Disord. 2006 Aug;94(1-3):183-9
16780958
Curr Med Res Opin. 2007 Feb;23(2):401-16
17288694
Obstet Gynecol. 2004 Sep;104(3):511-9
15339761
J Clin Psychopharmacol. 2004 Aug;24(4):389-99
15232330
BJU Int. 2007 Aug;100(2):337-45
17511767
Pain. 1995 Jan;60(1):91-102
7715946
Int J Gen Med. 2008 Nov 30;1:91-102
20428412
Psychol Med. 2009 Feb;39(2):267-76
18485261
Curr Med Res Opin. 2006 Nov;22(11):2121-9
17076972
Eur J Obstet Gynecol Reprod Biol. 2006 Mar 1;125(1):120-8
16188367
Psychopharmacol Bull. 2002 Autumn;36(4):106-32
12858150
Int J Neuropsychopharmacol. 2002 Dec;5(4):315-25
12466031
Pain. 2005 Jul;116(1-2):109-18
15927394
J Psychiatr Res. 2002 Nov-Dec;36(6):383-90
12393307
Prim Care Companion J Clin Psychiatry. 2007;9(2):100-7
17607331
Spine (Phila Pa 1976). 2010 Jun 1;35(13):E578-85
20461028
Neurology. 2006 Oct 24;67(8):1411-20
17060567
Int Urogynecol J Pelvic Floor Dysfunct. 2007 Aug;18(8):919-29
17160693
Am Fam Physician. 2007 Jul 15;76(2):247-54
17695569
Br J Clin Pharmacol. 2004 Jan;57(1):54-61
14678340
Prim Care Companion J Clin Psychiatry. 2004;6(2):65-73
15254599
Pain. 2009 Dec;146(3):253-260
19625125
Am J Obstet Gynecol. 2002 Jul;187(1):40-8
12114886
Psychiatry (Edgmont). 2007 Mar;4(3):39-45
20805909
BJOG. 2004 Mar;111(3):249-57
14961887
Pain. 2005 Dec 15;119(1-3):5-15
16298061
J Clin Psychiatry. 2002 Mar;63(3):225-31
11926722
Prog Drug Res. 2002;58:169-222
12079200
Hum Psychopharmacol. 2005 Jul;20(5):327-41
15912562
Curr Med Res Opin. 2007 Jan;23(1):175-84
17257478
J Clin Psychiatry. 2006;67 Suppl 6:3-8
16848670
Int Clin Psychopharmacol. 2005 Mar;20(2):59-69
15729080
BJOG. 2007 May;114(5):543-7
17355360
J Clin Psychiatry. 2002 Apr;63(4):308-15
12000204
BMC Urol. 2008 Jan 25;8:2
18221532
J Urol. 2003 Oct;170(4 Pt 1):1259-63
14501737
Pain. 2008 Jun;136(3):432-444
18395345
Pain Med. 2007 Sep;8(6):503-13
17716324
J Clin Psychopharmacol. 2008 Feb;28(1):32-8
18204338
Ann N Y Acad Sci. 1990;600:511-9; discussion 519-20
2252330
Depress Anxiety. 2008;25(3):182-9
17311303
Am J Psychiatry. 2007 Jun;164(6):900-9
17541049
Maturitas. 2008 Jun 20;60(2):138-47
18547757
Int Clin Psychopharmacol. 2007 May;22(3):167-74
17414743
J Psychiatr Res. 2005 Jan;39(1):43-53
15504423
Neuropsychopharmacology. 2001 Dec;25(6):871-80
11750180
J Urol. 2005 May;173(5):1647-53
15821528