Effectiveness of adjunctive antidepressant treatment for bipolar depression.
BACKGROUND
Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania.


METHODS
In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined.


RESULTS
Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups.


CONCLUSIONS
The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. (ClinicalTrials.gov number, NCT00012558 [ClinicalTrials.gov].).
Sachs
Gary S
GS
Bipolar Clinic and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. gsachs@partners.org
Nierenberg
Andrew A
AA
Calabrese
Joseph R
JR
Marangell
Lauren B
LB
Wisniewski
Stephen R
SR
Gyulai
Laszlo
L
Friedman
Edward S
ES
Bowden
Charles L
CL
Fossey
Mark D
MD
Ostacher
Michael J
MJ
Ketter
Terence A
TA
Patel
Jayendra
J
Hauser
Peter
P
Rapport
Daniel
D
Martinez
James M
JM
Allen
Michael H
MH
Miklowitz
David J
DJ
Otto
Michael W
MW
Dennehy
Ellen B
EB
Thase
Michael E
ME
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D016642:Bupropion / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000627:therapeutic use*; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D018692:Antimanic Agents; D016642:Bupropion; D017374:Paroxetine