Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone.
OBJECTIVE
Clinicians have few evidence-based options for the management of treatment-resistant bipolar depression. This study represents the first randomized trial of competing options for treatment-resistant bipolar depression and assesses the effectiveness and safety of antidepressant augmentation with lamotrigine, inositol, and risperidone.


METHODS
Participants (N=66) were patients with bipolar I or bipolar II disorder enrolled in the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). All patients were in a current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant. Patients were randomly assigned to open-label adjunctive treatment with lamotrigine, inositol, or risperidone for up to 16 weeks. The primary outcome measure was the rate of recovery, defined as no more than two symptoms meeting DSM-IV threshold criteria for a mood episode and no significant symptoms present for 8 weeks.


RESULTS
No significant between-group differences were seen when any pair of treatments were compared on the primary outcome measure. However, the recovery rate with lamotrigine was 23.8%, whereas the recovery rates with inositol and risperidone were 17.4% and 4.6%, respectively. Patients receiving lamotrigine had lower depression ratings and Clinical Global Impression severity scores as well as greater Global Assessment of Functioning scores compared with those receiving inositol and risperidone.


CONCLUSIONS
No differences were found in primary pairwise comparison analyses of open-label augmentation with lamotrigine, inositol, or risperidone. Post hoc secondary analyses suggest that lamotrigine may be superior to inositol and risperidone in improving treatment-resistant bipolar depression.
Nierenberg
Andrew A
AA
Massachusetts General Hospital Bipolar Clinic and Research Program, Suite 580, 50 Staniford Street, Boston, MA 02114, USA. anierenberg@partners.org
Ostacher
Michael J
MJ
Calabrese
Joseph R
JR
Ketter
Terence A
TA
Marangell
Lauren B
LB
Miklowitz
David J
DJ
Miyahara
Sachiko
S
Bauer
Mark S
MS
Thase
Michael E
ME
Wisniewski
Stephen R
SR
Sachs
Gary S
GS
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007294:Inositol / Q000627:therapeutic use*; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use*; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000627:therapeutic use
D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D014227:Triazines; D014803:Vitamin B Complex; D007294:Inositol; D018967:Risperidone; D000077213:Lamotrigine