Page 22 - e-book CPG - Bipolar Disorder
P. 22
CLINICAL PRACTICE GUIDELINES MANAGEMENT OF BIPOLAR DISORDER (2ND ED.)
4.1.2. Depressive episode
4.1.2. Depressive episode
4.1. 2 . D ep ressiv e epi so de
4.1.2. Depressive episode
Depressive episodes are debilitating for patients with BD and account for much of the time
Depressive episodes are debilitating for patients with BD and account for much of the time
D ep r essi v e ep i sod es a r e de bi l i t atin g f or pa t i en t s w i t h B D an d acco un t f o r m uch o f t he t i m e
Depressive episodes are debilitating for patients with BD and account for much of the time
spent unwell. This would include subsyndromal presentation and long-term functional
spent unwell. This would include subsyndromal presentation and long-term functional
spe nt un w el l . T hi s w ou l d i ncl ud e sub sy nd r o m al p r ese nta t i on an d l on g - t e r m f un ct i on al
spent unwell. This would include subsyndromal presentation and long-term functional
impairment. Management of depressive episodes in BD proves to be a challenging task given
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en
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impairment. Management of depressive episodes in BD proves to be a challenging task given
i
impairment. Management of depressive episodes in BD proves to be a challenging task given
the risk of treatment-emergent manic switch and increasing choices of treatment.
m
the risk of treatment-emergent manic switch and increasing choices of treatment. .
e
t
the risk of treatment-emergent manic switch and increasing choices of treatment.
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A network meta-analysis on bipolar depression comparing monotherapy vs placebo
ne
34, level I meta-analysis on bipolar depression comparing monotherapy vs placebo
w
t
or
A network meta-analysis on bipolar depression comparing monotherapy vs placebo
A
k
A network m eta - an al y si s on bi po l ar de pres si on co m pa r i n g m on othe r ap y v s pl ace bo
showed:
w
showed: : 3 34, level I I
showed:
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lev
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ed
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response rates were higher with tranylcypromine, venlafaxine, fluoxetine, imipramine,
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response rates were higher with tranylcypromine, venlafaxine, fluoxetine, imipramine, ,
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response rates were higher with tranylcypromine, venlafaxine, fluoxetine, imipramine,
valproate, olanzapine/fluoxetine combination (OFC), lurasidone, olanzapine, quetiapine,
al
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valproate, olanzapine/fluoxetine combination (OFC), lurasidone, olanzapine, quetiapine, ,
valproate, olanzapine/fluoxetine combination (OFC), lurasidone, olanzapine, quetiapine,
v
i
ne
,
ap
)
cariprazine and lamotrigine
ne
r
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cariprazine and lamotrigine
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ne
carip
cariprazine and lamotrigine
an
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remission rates were higher with tranylcypromine, fluoxetine, venlafaxine, OFC,
w
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remission rates were higher with tranylcypromine, fluoxetine, venlafaxine, OFC,
emissi
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r
remission rates were higher with tranylcypromine, fluoxetine, venlafaxine, OFC, ,
i
afax
quetiapine, lurasidone, olanzapine, lamotrigine
ap
urasi
i
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ap
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quetiapine, lurasidone, olanzapine, lamotrigine
quetiapine, lurasidone, olanzapine, lamotrigine
q
i
ol
an
z
,
ue
i
r
,
t
i
g
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amot
reduction in depression severity with fluoxetine, valproate, lurasidone, cariprazine,
reduction in depression severity with fluoxetine, valproate, lurasidone, cariprazine, ,
de
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proat
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etin
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erity
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reduction in depression severity with fluoxetine, valproate, lurasidone, cariprazine,
olanzapine and quetiapine
ap
t
an
d q
i
an
i
olanzapine and quetiapine
z
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i
olanzapine and quetiapine
ap
e
n
ue
ne
NS difference in discontinuation rate due to AEs for all medications except aripiprazole
t
al
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NS difference in discontinuation rate due to AEs for all medications except aripiprazole
i
du
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nu
s
NS difference in discontinuation rate due to AEs for all medications except aripiprazole
f
(OR=2.25, 95% CI 1.18 to 4.30) and quetiapine (OR=1.80, 95% 1.26 to 2.55)
%
95
(OR=2.25, 95% CI 1.18 to 4.30) and quetiapine (OR=1.80, 95% Cl 1.26 to 2.55)
(OR=2.25, 95% CI 1.18 to 4.30) and quetiapine (OR=1.80, 95% 1.26 to 2.55)
(
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Majority (74%) of the primary papers were of low risk of bias. 80 , 95 % 1.26 t o 2. 55 )
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Majority (74%) of the primary papers were of low risk of bias.
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r
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Majority (74%) of the primary papers were of low risk of bias.
A recent large network meta-analysis on adults with bipolar depression compared different
e
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a
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r
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35, level I depression compared different
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A recent large network meta-analysis on adults with bipolar
t
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t
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nt
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A recent large network meta-analysis on adults with bipolar depression compared different t
A
w
l
pressi
an
po
pharmacological treatments with placebo and reported:
pharmacological treatments with placebo and reported:
ph arm aco l o g i cal t r ea t m e nts w i t h pl ace bo an d r ep ort ed : 3 35, level I l I
,
lev
pharmacological treatments with placebo and reported:
e
5
35, level I
based on statistically significant effectiveness and good confidence evidence, the
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based on statistically significant effectiveness and good confidence evidence, the
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based on statistically significant effectiveness and good confidence evidence, the
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medications that improved depressive symptoms in MADRS, HAM-D (Hamilton
M
ns
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,
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sy
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i
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(
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medications that improved depressive symptoms in MADRS, HAM-D (Hamilton
medications that improved depressive symptoms in MADRS, HAM-D (Hamilton
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catio
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ptom
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pressi
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Depression Rating Scale), Inventory of Depressive Symptomatology (IDS) or Quick
al
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or
Depression Rating Scale), Inventory of Depressive Symptomatology (IDS) or Quick
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Depression Rating Scale), Inventory of Depressive Symptomatology (IDS) or Quick
Inventory of Depressive Symptomatology Self-Report (QIDS-SR) were OFC, quetiapine,
p
atol
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Q
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ptom
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Inventory of Depressive Symptomatology Self-Report (QIDS-SR) were OFC, quetiapine, ,
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R
t
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I
Inventory of Depressive Symptomatology Self-Report (QIDS-SR) were OFC, quetiapine,
g
el
o
e
en
r
S
O
-
w
v
f
olanzapine, lurasidone, lumateperone, cariprazine and lamotrigine.
olanzapine, lurasidone, lumateperone, cariprazine and lamotrigine.
olanzapine, lurasidone, lumateperone, cariprazine and lamotrigine.
olanzapine, lurasidone, lumateperone, cariprazine and lamotrigine.
quetiapine reduced the risk of manic switch (OR=0.49, 95% CI 0.33 to 0.75) while NS
)
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f
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t
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quetiapine reduced the risk of manic switch (OR=0.49, 95% CI 0.33 to 0.75) while NS
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t
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he
quetiapine reduced the risk of manic switch (OR=0.49, 95% CI 0.33 to 0.75) while NS
sk
49
r
risk was seen in all other individual drugs e.g. lithium, antiepileptics, antidepressants or
w
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as seen in
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risk was seen in all other individual drugs e.g. lithium, antiepileptics, antidepressants or
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risk was seen in all other individual drugs e.g. lithium, antiepileptics, antidepressants or
APs
APs
P
s
APs
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lumateperone (OR=2.71, 95% CI 1.29 to 5.71) and quetiapine (OR=1.99, 95% CI 1.51
(
=2
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1.29
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lumateperone (OR=2.71, 95% CI 1.29 to 5.71) and quetiapine (OR=1.99, 95% CI 1.51
d
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(
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lumateperone (OR=2.71, 95% CI 1.29 to 5.71) and quetiapine (OR=1.99, 95% CI 1.51
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to 2.63) had a higher risk of discontinuation due to AEs
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to 2.63) had a higher risk of discontinuation due to AEs
atio
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Overall quality assessment showed a 94% low risk of bias. E s
Overall quality assessment showed a 94% low risk of bias.
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Overall quality assessment showed a 94% low risk of bias.
In the third network meta-analysis on adults with bipolar depression treated with atypical
hi
s
si
po
w
ar
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aty
on
n
pressi
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s
et
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I In the third network meta-analysis on adults with bipolar depression treated with atypical
k
on
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pi
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36, level I depression treated with atypical
m
h
i
h
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In the third network meta-analysis on adults with bipolar
ated
t
r
w
cal
-
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or
ne
t
t
t
l
r
t
ul
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t
antipsychotic (AAP) monotherapy vs placebo revealed:
ed
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ve
36, level I
le
other
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psy
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pl
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antipsychotic (AAP) monotherapy vs placebo revealed:
P
i
an
m
)
ev
antipsychotic (AAP) monotherapy vs placebo revealed: : 3 36, level I I
r
on
significant improvement in MADRS was seen with lurasidone, olanzapine, quetiapine
ne
w
S
,
M
g
significant improvement in MADRS was seen with lurasidone, olanzapine, quetiapine
R
significant improvement in MADRS was seen with lurasidone, olanzapine, quetiapine
n
ue
A
si
q
D
i
t
,
urasi
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ne
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see
t
i
ap
as
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and cariprazine
i
praz
i
an
and cariprazine
ne
and cariprazine
d car
NS difference in discontinuation rate due to AEs among lurasidone, cariprazine,
carip
sco
f
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az
di
o
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s
ntin
i
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,
do
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ate
f
ne
ua
e
r
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on
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NS difference in discontinuation rate due to AEs among lurasidone, cariprazine,
NS difference in discontinuation rate due to AEs among lurasidone, cariprazine, ,
i
r
n
amon
g
ce
t
urasi
olanzapine and ziprasidone but significantly higher risk in aripiprazole and quetiapine
ne
an
y
d zip
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n a
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olanzapine and ziprasidone but significantly higher risk in aripiprazole and quetiapine
olanzapine and ziprasidone but significantly higher risk in aripiprazole and quetiapine
si
t
hi
i
i
ap
According to SUCRA analyses, lurasidone, olanzapine and quetiapine ranked first for
r
an
According to SUCRA analyses, lurasidone, olanzapine and quetiapine ranked first for
U
,
ap
urasi
t
f
al
l
R
ed
ne
t
A
i
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i
an
ccordi
According to SUCRA analyses, lurasidone, olanzapine and quetiapine ranked first for
an
f
ol
an
ue
ses,
ne
do
t
n
k
ng
q
e
s
C
d
i
y
i
or
o
ap
A
r
improvement in MADRS compared with placebo followed by cariprazine. Based on GRADE
carip
t
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prov
f
R
bo
E
h
D
R
i
az
M
S
ol
pl
G
r
m
co
B
ed
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i
ne
improvement in MADRS compared with placebo followed by cariprazine. Based on GRADE
ement
d
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.
m
ed
ace
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l
improvement in MADRS compared with placebo followed by cariprazine. Based on GRADE
on
by
n
r
i
ow
ase
w
i
assessment, both direct and indirect comparisons of the above AAPs for both outcomes were
en
ou
asse
A
w
es
di
assessment, both direct and indirect comparisons of the above AAPs for both outcomes were
assessment, both direct and indirect comparisons of the above AAPs for both outcomes were
h
or
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s
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t
t
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oth
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of moderate to high quality.
g
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o hi
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o of moderate to high quality. .
f
h
of moderate to high quality.
t
q
Two meta-analyses on adults with acute bipolar depression on mood stabilisers or APs,
an
Two meta-analyses on adults with acute bipolar depression on mood stabilisers or APs, ,
w
t
oo
l
p
Two meta-analyses on adults with acute bipolar depression on mood stabilisers or APs,
st
t
T
i
essi
l
r
s
-
po
ad
on
s
a
ar
P
ab
al
m
de
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ses
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r
e
w
o
on
t
t
on
i
y
sers
h
m
d
e
i
comparison between adjunctive of mainly second-generation antidepressants and placebo
comparison between
comparison between adjunctive of mainly second-generation antidepressants and placebo
compariso n be t w ee n ad j un ct i v e o f m a i nl y seco n d - g en era t i on an t i de pres san t s an d pl ace bo
37, level I;38, level I adjunctive of mainly second-generation antidepressants and placebo
showed:
w
ed
showed:
sho small reduction in depressive symptoms in the intervention group
showed:
:
,
lev
7
3
37, level I;38, level I
,
e
le
I
8
l
v
e
3
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l
;
37, level I;38, level I
t
nt
si
s
t
l
on
i
v
small reduction in depressive symptoms in the intervention group
al
m
ptom
uc
small reduction in depressive symptoms in the intervention group
en
he
erv
e sy
i
t
i
sm
group
r
i
es
i
on
n dep
n
r
ed
NS difference in response and remission
eren
f
esp
NS difference in response and remission
NS difference in response and remission
S
emissi
on
e and
r
ce in
f
r
on
di
s
N
NS difference in affective switch at short-term (up to 26 weeks) but a risk at long-term
k
w
k
t
r
on
i
t
s
N
at
a
NS difference in affective switch at short-term (up to 26 weeks) but a risk at long-term
(
S
u
ch
l
-
ec
n
-
o
a
f
e
sho
t
f
t
e
f
i
t
bu
t
erence
v
i
sw
NS difference in affective switch at short-term (up to 26 weeks) but a risk at long-term
p
i
m
er
)
at
26
s
r
g
m
f
di
r
t
ee
(52 weeks)
(
2
k
(52 weeks)
w
s
)
5
e
e
(52 weeks)
NS difference in patients with at least one AE
l
S
ce in
i
NS difference in patients with at least one AE
s
e
i
ea
eren
t
A
h at
t
N
di
en
st
pa
f
f
w
t
NS difference in patients with at least one AE
on
E
52.6% of included trials scored low risk on the measurement of the outcomes. Most of the
t
o
scored
ud
on
ncl
comes
t
f
i
m
t
m
f
52.6% of included trials scored low risk on the measurement of the outcomes. Most of the
52.6% of included trials scored low risk on the measurement of the outcomes. Most of the
52
ou
ost
ed
.
6%
o
ow
s
i
t
t
M
sure
r
r
s
he
.
t
en
al
i
o
l
k
ea
he
he
f
47.4% of studies that scored high risk were open-label studies.
en
op
es.
i
es
f
i
el
r
o
g
st
hi
ud
ud
h
ored
st
i
47.4% of studies that scored high risk were open-label studies.
4
l
7.4%
47.4% of studies that scored high risk were open-label studies.
ha
t
-
t
w
s
k
sc
ere
ab
8
8 8 8
8
