Mood stabilizers and antipsychotics for acute mania: a systematic review and
meta-analysis of combination/augmentation therapy versus monotherapy.
Author(s): Ogawa Y(1), Tajika A, Takeshima N, Hayasaka Y, Furukawa TA.
Affiliation(s): Author information:
(1)Department of Health Promotion and Human Behavior, Kyoto University Graduate
School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto,
606-8501, Japan, ogawa.yusuke.2u@kyoto-u.ac.jp.
Publication date & source: 2014, CNS Drugs. , 28(11):989-1003
BACKGROUND: Pharmacotherapy remains the mainstay of treatment for acute bipolar
mania, but there are many choices, including mood stabilizers (MSs) and
antipsychotics (APs).
OBJECTIVE: To provide an up-to-date and comprehensive review of the efficacy,
acceptability and adverse effects of MSs and APs as combination or augmentation
therapy versus monotherapy with either drug class for the treatment of acute
mania.
DATA SOURCES: The Cochrane Central Register of Controlled Trials, MEDLINE,
PsycINFO, Scopus, and clinical trial databases were searched for articles
published between the inception of the databases and July 1, 2014. The following
keywords were used: [bipolar disorder, mania, manic, mixed bipolar,
schizoaffective] combined with the names of MSs and APs. The reference lists of
all the identified randomized controlled trials (RCTs), articles that cited the
identified trials, and recent systematic reviews were also checked.
STUDY SELECTION: Double-blind RCTs comparing MS and AP as combination or
augmentation therapy with either monotherapy during the acute phase treatment of
mania were included in the present study. The electronic search yielded 6,445
potential articles in September 2013 and 264 new references in an updated search
performed in July 2014. Finally, 19 RCTs were considered eligible for our
meta-analyses: MS plus AP combination or augmentation therapy was compared with
MS monotherapy in 14 trials (n = 3,651) and with AP monotherapy in 6 trials
(n = 606) [one study compared combination therapy versus both MS monotherapy and
AP monotherapy].
DATA EXTRACTION: The primary outcomes were the mean change scores on validated
rating scales for mania and all-cause discontinuation at 3 weeks. The secondary
outcomes included response, remission, the mean change scores for depression,
dropouts due to adverse events and to inefficacy, and adverse events at 3 weeks
and mean change scores on validated rating scales at 1 week. Using random-effects
models, standardized mean difference (SMD), risk ratio (RR) and numbers needed to
treat with their 95 % confidence intervals (CIs) were calculated.
RESULTS: Most patients included in trials comparing combination/augmentation
therapy versus MS monotherapy had prior treatment with an MS, while more than
70 % of participants in trials comparing combination/augmentation therapy versus
AP monotherapy had not been on medications or were washed out from their previous
medication before randomization. MS plus AP combination/augmentation therapy was
more effective than MS monotherapy in terms of change in scores on mania rating
scales at 3 weeks (SMD -0.26; 95 % CI -0.36 to -0.15) and at 1 week (SMD -0.17,
-0.29 to -0.04). MS plus AP combination/augmentation therapy was more effective
than AP monotherapy at 3 weeks (SMD -0.31, -0.50 to -0.12), but not at 1 week
(SMD -0.22, -0.84 to 0.40). No significant differences were seen between the
combination/augmentation therapy and either monotherapy group in study withdrawal
for any reason (MS + AP vs. MS monotherapy: RR 0.99, 0.88-1.12; MS + AP vs. AP
monotherapy: RR 0.70, 0.47-1.04) or adverse events (MS + AP vs. MS monotherapy:
RR 1.39, 0.97-1.99; MS + AP vs. AP monotherapy: RR 0.62, 0.27-1.40). The
combination/augmentation therapy was associated with more side effects,
especially with somnolence, while it did not increase treatment-emergent
depression.
CONCLUSIONS: Combining MS and AP is more efficacious and more burdensome than,
but overall as acceptable as, the continuation of MS or AP monotherapy, when
either monotherapy has not been successful. There is currently no robust evidence
to judge whether MS and AP combination therapy is more efficacious than MS
monotherapy as the initial therapy for acutely manic patients without prior
medication.
|