Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression.
OBJECTIVE
This study compared the efficacy and safety of paroxetine and imipramine with that of placebo in the treatment of bipolar depression in adult outpatients stabilized on a regimen of lithium.


METHODS
In a double-blind, placebo-controlled study, 117 outpatients with DSM-III-R bipolar disorder, depressive phase, were randomly assigned to treatment with paroxetine (N=35), imipramine (N=39), or placebo (N=43) for 10 weeks. In addition to lithium monotherapy, patients may have received either carbamazepine or valproate in combination with lithium for control of manic symptoms. Patients were stratified on the basis of trough serum lithium levels determined at the screening visit (high: >0.8 meq/liter; low: </=0.8 meq/liter). Primary efficacy was assessed by change from baseline in scores on the Hamilton Rating Scale for Depression and the Clinical Global Impression illness severity scale.


RESULTS
Differences in overall efficacy among the three groups were not statistically significant. For patients with high serum lithium levels, antidepressant response at endpoint also did not significantly differ from placebo. However, both paroxetine and imipramine were superior to placebo for patients with low serum lithium levels. Compared to imipramine, paroxetine resulted in a lower incidence of adverse events, most notably emergence of manic symptoms.


CONCLUSIONS
Antidepressants may not be useful adjunctive therapy for bipolar depressed patients with high serum lithium levels. However, antidepressant therapy may be beneficial for patients who cannot tolerate high serum lithium levels or who have symptoms that are refractory to the antidepressant effects of lithium.
Nemeroff
C B
CB
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Dr., Suite 4000, Atlanta, GA 30322, USA.
Evans
D L
DL
Gyulai
L
L
Sachs
G S
GS
Bowden
C L
CL
Gergel
I P
IP
Oakes
R
R
Pitts
C D
CD
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000927:Anticonvulsants / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D002220:Carbamazepine / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use*; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000627:therapeutic use*; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D002220:Carbamazepine; D007099:Imipramine; D008094:Lithium; D017374:Paroxetine; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D014635:Valproic Acid