Duloxetine For The Treatment Of Generalized Social Anxiety - MBL ...

dose change. It is worth noting that a large multicenter
randomized controlled study of duloxetine
in adults with MDD similarly reported no
advantage of increasing the dose to 120 mg/day
compared to continued 60 mg/day for an additional
8 weeks in subjects who did not achieve
remission after 6 weeks. 21
Importantly, there are also likely finer measures
of change clinicians may employ than the
binary assessment of remission status we used
in this trial when deciding whether to maintain
or change a specific medication and dose at a
given time. For example, while Phase 1 reduction
in LSAS was minimally associated with
Phase 2 LSAS reduction, slope of change in a
variety of variables such as mood, level of function,
and GSAD symptoms may be important in
predicting who may respond best to an increase
in dose. Further, some individuals with the
greatest reduction in LSAS who achieved remission
by week 6 were not randomized into Phase
2, and thus the possible range for week 6 LSAS
improvement examined as a predictor of Phase
2 LSAS change was truncated by design. This
may in part explain the lack of significant association
of Phase 1 change with Phase 2 change.
Our power was too limited to examine the moderating
effect of these clinical features on differential
response, but would be of interest in
future study. Further, conclusions from this trial
are limited to a sample of treatment-seeking
patients with primary, generally chronic, GSAD.
Another limitation is the relatively high overall
drop-out rate, at 44%. However, this is comparable
to other 6-month trials of pharmacotherapy for
GSAD, including a trial with venlafaxine in which
57% did not complete the full 28 weeks. 5 The overall
study discontinuation due to adverse events of
21% (8/39) with duloxetine in the current trial was
also comparable to the 21% rate in the 6-month
venlafaxine trial with higher doses (venlafaxine
XR 150–225 mg/day), 5 and comparable to the 15%
rate reported in the combined large, randomized
controlled trials of duloxetine for GAD. 22 Notably,
there was no difference in rates of discontinuation
between the two randomized duloxetine dose
level treatment arms. Our experience with initiation
side effects with 60 mg/day in this trial suggests
it may be best to initiate duloxetine at 30
mg/day and titrate the dose gradually for individuals
with GSAD, consistent with general clinical
experience with other antidepressants in the treatment
of anxiety disorders.
Original Research
CONCLUSION
Although power was limited and larger, and
randomized placebo-controlled trials are needed,
these data provide preliminary support for the
potential efficacy of duloxetine for GSAD, and suggest
continued improvement at 24 weeks for individuals
who are symptomatic at week 6. Increasing
the dose to 120 mg/day at 6 weeks versus continuing
60 mg/day did not result in a significantly
greater improvement, but was suggestive of
greater efficacy at the level of a moderate effect
size. Tolerability results suggest that initiation at
lower doses (ie, 30 mg) and slower dose titration
may be beneficial in this population. CNS
REFERENCES
1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence
and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey
Replication. Arch Gen Psychiatry. 2005;62(6):593-602.
2. Van Ameringen MA, Lane RM, Walker JR, et al. Sertraline treatment of generalized
social phobia: a 20-week, double-blind, placebo-controlled study. Am J Psychiatry.
2001;158(2):275-281.
3. Stein MB, Liebowitz MR, Lydiard RB, Pitts CD, Bushnell W, Gergel I. Paroxetine treatment
of generalized social phobia (social anxiety disorder): a randomized controlled trial. JAMA.
1998;280(8):708-713.
4. Stein MB, al. e. Efficacy of low and higher dose extended-release venlafaxine in generalized
social anxiety disorder: a 6-month randomized controlled trial. Psychopharmacology.
2005;177(3):280-288.
5. Stein MB, Pollack MH, Bystritsky A, Kelsey JE, Mangano RM. Efficacy of low and higher
dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized
controlled trial. Psychopharmacology. 2005;177(3):280-288.
6. Liebowitz MR, Stein MB, Tancer M, Carpenter D, Oakes R, Pitts CD. A randomized, doubleblind,
fixed-dose comparison of paroxetine and placebo in the treatment of generalized
social anxiety disorder. J Clin Psychiatry. 2002;63(1):66-74.
7. Dunner DL, Goldstein DJ, Mallinckrodt C, Lu Y, Detke MJ. Duloxetine in treatment of anxiety
symptoms associated with depression. Depress Anxiety. 2003;18(2):53-61.
8. Fava M, Martinez JM, Greist J, et al. The efficacy and tolerability of duloxetine in the
treatment of anxious versus non-anxious depression: a post-hoc analysis of an open-label
outpatient study. Ann Clin Psychiatry. 2007;19(3):187-195.
9. Koponen H, Allgulander C, Erickson J, et al. Efficacy of duloxetine for the treatment of
generalized anxiety disorder: implications for primary care physicians. Prim Care Companion
J Clin Psychiatry. 2007;9(2):100-107.
10. Crippa JA, Filho AS, Freitas MC, Zuardi AW. Duloxetine in the treatment of social anxiety
disorder. J Clin Psychopharmacol. 2007;27(3):310.
11. Lin CC. Duloxetine treatment of social anxiety disorder with comorbid major depression. J
Clin Psychopharmacol. 2008;28(5):591-592; author reply 592-593.
12. Scott EL, Pollack MH, Otto MW, Simon NM, Worthington JJ. Clinician response to treatment
refractory panic disorder: a survey of psychiatrists. J Nerv Ment Dis. 1999;187(12):755-757.
13. First MS, Gibbon M, Williams JBW. Structured Clinical Interview for Axis I DSM-IV
Disorders - Patient version (SCID-1/P version 2.0). New York, NY: New York State Psychiatric
Institute Biometrics Research Department; 1994.
14. Doyle AC, Pollack MH. Establishment of remission criteria for anxiety disorders. J Clin
Psychiatry. 2003;64(Suppl 15):40-45.
15. Ballenger JC. Clinical guidelines for establishing remission in patients with depression and
anxiety. J Clin Psychiatry. 1999;60(Suppl 22):29-34.
16. Sheehan DV, Harnett-Sheehan K, Raj BA. The measurement of disability. Int Clin
Psychopharmacol. 1996;11(Suppl 3):89-95.
17. Endicott J, Nee J, Harrison W, Blumenthal R. Quality of Life Enjoyment and Satisfaction
Questionnaire: a new measure. Psychopharmacol Bull. 1993;29(2):321-326.
18. Rapaport MH, Davidson JR. The efficacy of new pharmacological treatments for panic
disorder: evaluating the trials. Psychopharmacol Bull. 1998;34(2):167-168.
19. Schneier FR, Heckelman LR, Garfinkel R, et al. Functional impairment in social phobia. J Clin
Psychiatry. 1994;55(8):322-331.
20. Davidson JR. Pharmacotherapy of social anxiety disorder: what does the evidence tell us? J
Clin Psychiatry. 2006;67(Suppl 12):20-26.
21. Kornstein SG, Dunner DL, Meyers AL, et al. A randomized, double-blind study of increasing
or maintaining duloxetine dose in patients without remission of major depressive disorder
after initial duloxetine therapy. J Clin Psychiatry. 2008;69(9):1383-1392.
22. Cymbalta delayed-release capsules. In: Physician’s Desk Reference. 63rd ed. Montvale,
NJ: Thomson PDR; 2009.
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