Antidepressant discontinuation in bipolar depression: a Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) randomized clinical trial of long-term effectiveness and safety.
OBJECTIVE
To assess long-term effectiveness and safety of randomized antidepressant discontinuation after acute recovery from bipolar depression.


METHODS
In the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, conducted between 2000 and 2007, 70 patients with DSM-IV-diagnosed bipolar disorder (72.5% non-rapid cycling, 70% type I) with acute major depression, initially responding to treatment with antidepressants plus mood stabilizers, and euthymic for 2 months, were openly randomly assigned to antidepressant continuation versus discontinuation for 1-3 years. Mood stabilizers were continued in both groups.


RESULTS
The primary outcome was mean change on the depressive subscale of the STEP-BD Clinical Monitoring Form. Antidepressant continuation trended toward less severe depressive symptoms (mean difference in DSM-IV depression criteria = -1.84 [95% CI, -0.08 to 3.77]) and mildly delayed depressive episode relapse (HR = 2.13 [1.00-4.56]), without increased manic symptoms (mean difference in DSM-IV mania criteria = +0.23 [-0.73 to 1.20]). No benefits in prevalence or severity of new depressive or manic episodes, or overall time in remission, occurred. Type II bipolar disorder did not predict enhanced antidepressant response, but rapid-cycling course predicted 3 times more depressive episodes with antidepressant continuation (rapid cycling = 1.29 vs non-rapid cycling = 0.42 episodes/year, P = .04).


CONCLUSIONS
This first randomized discontinuation study with modern antidepressants showed no statistically significant symptomatic benefit with those agents in the long-term treatment of bipolar disorder, along with neither robust depressive episode prevention benefit nor enhanced remission rates. Trends toward mild benefits, however, were found in subjects who continued antidepressants. This study also found, similar to studies of tricyclic antidepressants, that rapid-cycling patients had worsened outcomes with modern antidepressant continuation.


BACKGROUND
clinicaltrials.gov Identifier: NCT00012558.
Ghaemi
S Nassir
SN
Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, 800 Washington St, Box 1007, Boston, MA 02111, USA. nghaemi@tuftsmedicalcenter.org
Ostacher
Michael M
MM
El-Mallakh
Rif S
RS
Borrelli
David
D
Baldassano
Claudia F
CF
Kelley
Mary E
ME
Filkowski
Megan M
MM
Hennen
John
J
Sachs
Gary S
GS
Goodwin
Frederick K
FK
Baldessarini
Ross J
RJ
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001294:Attitude to Health; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000453:epidemiology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011569:Psychiatric Status Rating Scales; D012449:Safety; D055502:Secondary Prevention; D017367:Selective Serotonin Reuptake Inhibitors; D016019:Survival Analysis; D016896:Treatment Outcome
D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D016651:Lithium Carbonate; D017367:Selective Serotonin Reuptake Inhibitors