Treatment-emergent mania/hypomania during antidepressant monotherapy in patients with rapid cycling bipolar disorder.
OBJECTIVE
To study treatment-emergent mania/hypomania (TEM) associated with second-generation antidepressant monotherapy in patients with rapid cycling bipolar disorder (RCBD).


METHODS
Data of patients with RCBD (n = 180) enrolled into two clinical trials were used to study the risk for TEM during second-generation antidepressant monotherapy. History of TEM was retrospectively determined at the initial assessment by asking patients whether they were exposed to second-generation antidepressants and if a hypomania/mania episode emerged during the first four weeks of treatment. Data were analyzed using t-test, chi-square, and logistic regression.


RESULTS
Of the 180 patients (bipolar I disorder, n = 128; bipolar II disorder, n = 52) with RCBD, 85% (n = 153) had at least one antidepressant treatment. Among these patients, 94.1% (144/153) had at least one antidepressant monotherapy treatment. Overall, 49.3% of patients had at least one TEM and 29.1% (116/399) of treatment trials were associated with TEM. In regression analysis, an inverse association between the number of mood episodes in the last 12 months and TEM was observed with an odds ratio of 0.9. However, gender, bipolar subtype, a lifetime history of comorbid anxiety disorder, substance use disorder, or psychosis, and age of mood disorder onset were not associated with TEM. For individual antidepressants, the rates of TEM varied from 42.1% for fluoxetine to 0% for fluvoxamine and mirtazapine. As a group, there was no difference between selective serotonin reuptake inhibitors and venlafaxine or bupropion in the incidence of TEM.


CONCLUSIONS
Use of second-generation antidepressants as monotherapy in RCBD is accompanied by clinically relevant rates of TEM. Even in patients with RCBD, differential vulnerabilities to antidepressant TEM may exist.
Gao
Keming
K
Department of Psychiatry, Bipolar Disorder Research Center at Mood Disorders Program, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, 10524 Euclid Avenue, Cleveland, OH 44106, USA. keming.gao@uhhospitals.org
Kemp
David E
DE
Ganocy
Stephen J
SJ
Muzina
David J
DJ
Xia
Guohua
G
Findling
Robert L
RL
Calabrese
Joseph R
JR
D000328:Adult; D000339:Affect / Q000187:drug effects*; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015897:Comorbidity; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000077213:Lamotrigine; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000523:psychology; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use
D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D018692:Antimanic Agents; D005473:Fluoxetine; D000077213:Lamotrigine; D016651:Lithium Carbonate; D017367:Selective Serotonin Reuptake Inhibitors; D014227:Triazines; D014635:Valproic Acid