Original article 257
Jay D. Amsterdama and Justine Shultsb
monotherapy of bipolar type II and bipolar
a double-blind, placebo-substitution,
However, this difference was not clinically meaningful. No
hypomanic switch episodes were observed during study
phase II. Despite the limited sample size resulting in
insufficient power to detect statistical significance
relapse rates or change in YM R scores between treatment
conditions, these preliminary data appear to support
previous observations demonstrating
continuation fluoxetine monotherapy
effective for some patients with BP II or BP NOS MDE
with a low manic switch rate. Larger-scale studies are
needed to confirm these findings. Int Clin Psychopharmacol
20:257-264 @ 2005 Lippincott Williams & Wilkins.
patients (0.2:t 0.4) (P= 0.01).
that initial and
may be safe and
International Clinical Psychopharmacology 2005, 20:257-264
manic switch episode, SSRI
therapy, bipolar depression, bipolar type II
"Depression Research Unit, Department of Psychiatry and bCenter for Clinical
Epidemiology and Bio-statistics, University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania, USA.
Research Unit, University Science Center, Third Floor, 3535 Market Street,
Philadelphia, PA 19104, USA.
Tel: + 1 2156623462; fax: + 1 2156626443;
and requests for reprints to Jay D. Amsterdam, Depression
Current guidelines for the treatment of bipolar type II
(BP II) major depressive episode (MDE) recommend using
either mood stabilizer monotherapy or the combination
of a mood stabilizer with a selective serotonin reuptake
inhibitor (SSRI). These guidelines are the result of concern
over SSRI-induced manic switch episodes. We previously
showed that fluoxetine monotherapy
an initial treatment for BP II and BP NOS MDE with
a low manic switch rate. We now present the results of a
fluoxetine monotherapy in BP II and BP NOS patients who
have recovered from their MDE. This was a two-phase
study. In study phase I, patients received open-label
fluoxetine monotherapy 20 mg daily for up to 8 weeks.
Responders with a final 17-item Hamilton Rating Scale
for Depression (HAM-D) score ~ 9 were enrolled into
study phase II which consisted of double-blind,
20 mg daily for up to 6 months. Outcome measures
included the 17-item HAM-D and Young Mania Rating
(YMR) scales. Changes in YMR scores were assessed
using generalized estimating
was assessed using Kaplan-Meier
and Fisher's exact test. In study phase 11,43% of
fluoxetine-treated patients and 100% of placebo-treated
patients relapsed during continuation
The mean increase in YMR score in study phase II was
slightly higher in the fluoxetine-treated
may be effective as
continuation study of
therapy with fluoxetine
equation analysis. Relapse
patients (3.0:t 1.8)
Received 28 September 2004 Accepted 1 8 May 2005
consider them to be in need of treatment (Cassano et ai,
1999) and, as a result, BP II disorder is generally diagnosed
when the patient seeks treatment for a major depressive
episode (MDE) (Benazzi, 1997; Cassano et ai, 1999;
Ghaemi et al, 2001). The incidence of BP II MDE may
vary widely depending upon the ascertainment method
used (Benazzi, 1997; Goodwin and Ghaemi, 1998; Ghaemi
et ai, 1999; Ghaemi et aL, 2000). Surveys of clinical
populations have found the rates of BP II disorder to be as
high as 45% of patients who were previously diagnosed with
unipolar MDE (Benazzi, 1997; Goodwin and Ghaemi,
1998). This is largely the result of a failure to recognize
previous hypomanic episodes that can frequently be of
short duration and characterized by an enhanced sense of
well-being, or by symptoms of irritability and agitation.
These brief hypomanic episodes stand in stark contrast to
the more frequent and prolonged BP II MDEs.
Bipolar type II (BP II) disorder is the most common
phenotype of BP disorder (Simpson t't ol, 1993; Benazzi
et 01., 1997; Akiskal and Pinto, 1999; Benazzi, 1999;
Akiskal, 2003; Berk and Dodd, 2005). Its clinical course is
characterized by a preponderance of depressive episodes
with a lifetime history of one or more hypomanic episodes
lasting at least 4 days (Dunner et ol, 1976; Akiskal, 1996).
BP II disorder is diagnostically stable over time (Akiskal,
1996, 2003) and rarely evolves into 'BP type I (manic-
depressive) disorder (Ayuso-Gutierre?; and Ramos-Brieva,
1982; Faedda et ol, 1993; Coryell et ol, 1995). BP II
disorder is often difficult to recognize, and frequently
goes undiagnosed (Benazzi, 1997, 1 <)99; Cassano et ol,
1999; Akiskal, 2003; Goldberg, 2003; Berk and Dodd,
2005). BP II patients often do not rec<?gnize
of their hypomanic symptoms or, if recbgnized, they rarely
0268-1315 @ 2005 Lippincott Williams & Wilkins
264 International Clinical Psychopharmacology 2005, Vol 20 No 5
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