Erin Jackson

Ms. Kucik
Independent Research
24 March 2016
Meta-Analysis
List of Studies Used:

Baumer, Fiona M., Meghan Howe, Kim Gallelli, Diana Iorgova Simeonova, Joachim
Hallmayer, and Kiki D. Chang. "A Pilot Study of Antidepressant-Induced Mania in
Pediatric Bipolar Disorder: Characteristics, Risk Factors, and the Serotonin Transporter
Gene." Biological Psychiatry 60.9 (2006): 1005-012. Juvenile Bipolar Research
Foundation. Web. Feb. 2016. <http://www.jbrf.org/wpcontent/uploads/Baumer_BP_2006_TEM.pdf>.
Biederman, Mick, Hamerness Et. Al. "Open Label 8 Week Trial of Olanzapine and
Risperidone for the Treatment of Bipolar Disorder in Preschool-Aged Children."
National Center for Biotechnology Information. U.S. National Library of Medicine, n.d.
Web. 07 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/16239162>.
Bobo, Cooper, Stein Et. Al. "Antipsychotics and the Risk of Type 2 Diabetes." Journal of
American Medical Association 70.10 (2013): 1067-075. JAMA Network. Web. 07 Apr.
2016. <http://archpsyc.jamanetwork.com/article.aspx?articleid=1731662>.
Findling, Mcnamara, Stansbrey. "Combination Lithium and Divalproex Sodium."
American Academy of Child and Adolescent Psychiatry 45.2 (2006): 142-48. Eric
Youngstrom. University of North Carolina, Chapel Hill. Web. Feb. 2016.
<http://ericyoungstrom.web.unc.edu/files/2013/09/Findling-et-al.-2006-Phase-IIIrestabilization-20649.pdf>.
Findling, Robert L., Nora K. McNamara, Eric A. Youngstrom, Robert J. Stansbrey,
Thomas W. Frazier, Jacqui Lingler, Benjamin D. Otto, Christine A. Demeter, Brieana M.
Rowles, and Joseph R. Calabrese. "An Open-Label Study of Aripiprazole in Children
with a Bipolar Disorder." Journal of Child and Adolescent Psychopharmacology 21.4
(2011): 345-51. National Center for Biotechnology Information. U.S. National Library of
Medicine. Web. 07 Apr. 2016.
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192054/>.
Geller, Barbara, Joan L. Luby, Paramjit Joshi, Karen Dineen Wagner, Graham Emslie,
John T. Walkup, David A. Axelson, Kristine Bolhofner, Adelaide Robb, Dwight V. Wolf,
Mark A. Riddle, Boris Birmaher, Nasima Nusrat, Neal D. Ryan, Benedetto Vitiello,
Rebecca Tillman, and Philip Lavori. "A Randomized Controlled Trial of Risperidone,
Lithium, or Divalproex Sodium for Initial Treatment of Bipolar I Disorder, Manic or
Mixed Phase, in Children and Adolescents." Journal of American Medical Association
96.5 (2012): 515-28. Archives of General Psychiatry. U.S. National Library of Medicine.
Web. 07 Apr. 2016. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581342/>.
Kemp, David E., Keming Gao, Stephen J. Ganocy, Daniel J. Rapport, Omar Elhaj, Sarah
Bilali, Carla Conroy, Robert L. Findling, and Joseph R. Calabrese. "A 6-Month, DoubleBlind, Maintenance Trial of Lithium Monotherapy Versus the Combination of Lithium
and Divalproex for Rapid-Cycling Bipolar Disorder and Co-Occurring Substance Abuse
or Dependence." The Journal of Clinical Psychiatry 70.1 (2009): 113-21. National

Center for Biotechnology. U.S. National Library of Medicine, 4 Mar. 2013. Web. 07 Apr.
2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587136/>.
Pavuluri, Mani N., David B. Henry, Robert L. Findling, Stephanie Parnes, Julie A.
Carbray, Tahseen Mohammed, Philip G. Janicak, and John A. Sweeney. "Double-Blind
Randomized Trial of Risperidone versus Divalproex in Pediatric Bipolar Disorder."
Bipolar Disorders 12.6 (2010): 593-605. National Center for Biotechnology Information.
U.S. National Library of Medicine, 3 Jan. 2011. Web. 07 Apr. 2016.
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013630/>.
Sachs, Nierenberg, Calabrese Et. Al. "Effectiveness of Adjunctive Antidepressant
Treatment for Bipolar Depression NEJM." The New England Journal of Medicine 356
(2007): 1711-722. New England Journal of Medicine. Web. 07 Apr. 2016.
<http://www.nejm.org/doi/full/10.1056/nejmoa064135#t=articleResults>.
Tohen, Vieta, Calabrese Et. Al. "Efficacy of Olanzapine and Olanzapine-Fluoxetine
Combination in the Treatment of Bipolar I Depression." The Journal of American
Medical Association 60.11 (2003): 1079-088. JAMA Network. Web. 07 Apr. 2016.
<http://archpsyc.jamanetwork.com/article.aspx?articleid=208020>.

Method
Materials
I used at least one separate study for each category of medicine. When I was searching for
studies on antipsychotics, antidepressants and mood stabilizers, I ensured I had multiple
medications within each category.I needed a way to organize my data, so I made a chart. Peer
reviewed journals published all of the studies I used. I attached a list of the studies I used to do
my research.
Procedure
My method was first choosing at least one study for each medicine. I wanted to study
antidepressants, antipsychotics and mood stabilizers, which are all medicines used to treat
bipolar disorder. I analyzed each study, looking for specific information. The first piece of data, I
searched for was the success or response rate and then I tried to find whether it improved mania
or depression. I then searched for a correlation between the medicine and it inducing mania or
depression. I also looked at the age range of patients in the study, how long the patients were on
the medicine and the sample size. After, I filled in my miscellaneous section where I wrote down
information I thought might be important. Next, I needed to organize my data and make it easier
to analyze my results, so I made tables and graphs.
Results
Treatment and
Category

Risperidone
Antipsychotic

Sa
Ti
mpl me
e
Size

66

Ag
e
Ra
nge

6
8wks 18

Succe
ss
Rate
Perce
ntage

Mani
a
Impr
oved

Mani
c
Symp
toms

Depre
ssive
sympt
oms

Depres
sion
Impro
ved

Side
effects/ri
sks

Respo
nse
rate
(meas
ured
w/
YMR
S):
78.1%
Slope
was
-8.29

62.5
%
remis
sion

No

No

Yes,
rate of
change
for
linear
regress
ion was
-5.1

Found it
treated
depressi
ve
symptom
s
Did not
find
significa
nt
differenc
e in
metaboli
c side
effects.
Only six
weeks so

may not
have
taken it
long
enough
to have
side
effects
89

Study analyzing
risks

8
6
wee to
ks
15

Respo
nse
Rate
was
68.5%
for
mania

Yes

No

No

No

Found
Risperid
one was
more
effective
initially
but
caused
worse
metaboli
c side
effects
Increase
d weight
gain,
BMI and
prolactin
level
15.7%
discontin
uation
rate

Min 6
.1
to
yea 24
r
per
pati
ent
(1/9
612/
07)

N/A

N/A

N/A

N/A

N/A

Caused
increased
weight
gain,
BMI,
increased
glucose
level and
insulin
resistanc
e
Up to 1
year

after
stopping
antipsyc
hotics
Lithium
Mood Stabilizer

Combination
Lithium and
Divalproex Sodium
Mood Stabilizers

90

8
6
wee to
ks
15

Respo
nse
rate
was
35.6%

149

6
16
mo to
nths 65

149

6
16
mo to
nths 65

Yes

No

N/A

Yes

Higher
than
discontin
uation
rate than
risperido
ne
Increase
d
thyrotrop
in level
(higher
metaboli
sm)
32.2%
discontin
uation
rate

12%
Yes
did not
respon
d

Yes
Yes
40%
13%
(Relap
sed)

Yes

15.9
weeks
before a
relapse/
mood
episode

13%
Yes
did not
respon
d

Yes
40%

Yes

17.8
weeks
before a
relapse/
mood
episode
19%
discontin
ued

Yes
13%

Divalproex
Sodium
Anticonvulsant
mood stabilizer

Aripiprazole
Antipsychotic

Olanzapine
Antipsychotic

66

6
8
wks to
18

Respo
nse
rate
(meas
ured
w/
YMR
S)
45.5%
slope
was
-7.12

Yes

No

No

Yes,
rate of
change
for
linear
regress
ion was
-5.1

Had a
lower
slope
than
risperido
ne but
eventuall
y evened
out w/o
side
effects

100

8
6
wee to
ks
15

Respo
nse
Rate
was
24%

Yes
24 %

No

N/A
(treatin
g
mania)

Had a
low
initial
response
rate.

96

12. 4-9
5
wee
ks

62.5%
respon
ded

Yes

No

No

Yes

Side
effects
were
stomach
aches,
headache
s and
increased
appetite
Good
response
rate.
Initially
quicker.

370

8
Ad Yes
wee ults depres
ks
sion
impro
ved

No

Only
No
5.7%
develo
ped
mania

Signifi
cantly
more
effectiv
e than
placeb
o

51%
discontin
ued
Only 8
weeks
may not
have had
time to
develop
mania

Sertraline
Antidepressant

179

26
Ad 23.5%
wee ults succes
ks
s rate

No

Only
No
10.1%

Less
effectiv
e than
placeb
o that
had
27%
success
rate

OlanzapineFluoxetine
Antipsychotic/A
ntidepressant
(SSRI)

86

8
Ad Yes
wee ults depres
ks
sion
impro
ved

Yes

Only
No
6.4%
develo
ped
mania

Signifi
cantly
more
effectiv
e than
placeb
o

36%
discontin
ued
Only 8
weeks
Only 8
weeks
may not
have had
time to
develop
mania
Also
used
antipsyc
hotic

Bupropion
Antidepressant

36

6
Ad Yes
wee ults depres
ks
sion
impro
ved

Yes

No
No
(not a
signifi
cant
rate)

Yes

17%
discontin
ued
It was
only a 6
week
trial so
there
was not
a lot of
time for
mania to
develop
Also a
very
small
sample
size

My data suggests that antipsychotics are the medicine with the highest initial response
rate. My data also shows that none of my medicines seem to induce mania or depression. I also

found some of the antidepressants to not be particularly effective. Sertraline only had a 23%
success rate as opposed to the placebo which had a 27% success rate. Bupropion, an
antidepressant had some success in treating mania because it is a newer antidepressant. Overall,
antidepressants do not seem to have success treating mania on their own, however they do not
seem to induce mania. My data demonstrates that antipsychotics do not induce mania and there
are higher relapse rates with mood stabilizers. I also saw that antipsychotics and mood stabilizers
seemed to treat depression and mania. Mood stabilizers have a lower success rate and
antidepressants have the lowest.
Discussion
My data suggests antipsychotics seem to have the highest initial response rate,
antidepressants do not induce mania and mood stabilizers seem to have high relapse rates
meaning patients seem to have mania Also some of my results surprised me. I was shocked to
find antidepressants did not induce mania. None of my studies on any antidepressants showed
that they induced mania or if they did it was only a small percentage. I have read many articles
that showed antidepressants induced mania, but then I realized that almost all of my studies were
mainly short term and would probably take more time for the patients to start displaying manic
symptoms. Antidepressants increase serotonin, norepinephrine or dopamine levels. Mania
happens when there are an excess of these neurotransmitters. As a result, it makes scientific
sense that antidepressants could induce mania.
My hypothesis that mood stabilizers are more effective than antipsychotics and
antidepressants at treating bipolar disorder in children and adolescents was not supported.. I
think is because my studies were mostly short term. Throughout my research, I learned that
mood stabilizers would take a longer time to work. I think that if I found more long term studies,
I would find mood stabilizers have about the same success rate as antipsychotics but with less
side effects. I think mood stabilizers seemed to have a higher relapse rate because they are more
hit or miss medicines, which I was expecting. The different types of mood stabilizers target
certain neurotransmitters. I think once a patient is treated with the right mood stabilizers, it
would be the best option because they bring less side effects and over time will have about the
same success rate.
One problem I had with my studies were that they were mostly over a short period time meaning
6 to 8 weeks. I only had one study were patients took medicine for a year and found two studies
where patients took the medicine for six months. Even this is a relatively short time period, when
I am looking for medicine that would be the most effective in the long term. However, the time is
a variable I could not control as I had to find free studies that had the data I needed. I think
another issue with my data is that I had a small sample of studies. The maximum number of
studies for each medicine was three and to get the most accurate data, I needed to have more.
However, I was limited by time and cost.