Treatment-Resistant Bipolar Depression: A STEP-BD Equipoise Randomized Effectiveness Trial of Antidepressant Augmentation With Lamotrigine, Inositol, or Risperidone.
Patients with bipolar disorder, currently in a major depressive episode that was not responsive to mood stabilizer plus at least one antidepressant, received one of three augmentation treatments: lamotrigine, inositol, or risperidone. Equipoise randomization limited the statistical power of this study. While rates of recovery between the treatments did not achieve statistical significance, secondary outcome measures suggest that lamotrigine may be superior to inositol or risperidone.
- The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was funded by the NIMH to evaluate longitudinal outcomes of patients with bipolar disorder.
- N=66, adults with bipolar I or II, currently in major depressive episode that was nonresponsive to combination mood stabilizer plus antidepressant were assigned to up to 16 weeks of open-label adjunctive treatment with:
- Lamotrigine (n=21)
- Inositol (n=23)
- Risperidone (n=22)
- Equipoise randomization was used, in which the patient and clinician were allowed to eliminate one of the three treatment options from consideration. This was necessary for recruitment, as many patients had tried one treatment in the past and found it unacceptable. Only three of the 66 patients opted to be randomized to all three options. Equipoise randomization limited the statistical power of this study.
- Primary outcome: rate of recovery, defined as no more than two DSM-IV mood episode criteria and no significant symptoms for 8 weeks.
- Recovery rate did not differ significantly (95% CI):
- 23.8% (5.8-41.8) with lamotrigine
- 17.4% (2.4-32.4) with inositol
- 4.6% (0-14.6) with risperidone
- Lamotrigine was associated with lower depression ratings, lower CGI (Clinical Global Impression) severity scores, and higher Global Assessment of Functioning scores.
Nierenberg AA, Ostacher MJ, Calabrese JR, et al. Treatment-Resistant Bipolar Depression: A STEP-BD Equipoise Randomized Effectiveness Trial of Antidepressant Augmentation With Lamotrigine, Inositol, or Risperidone. AJP. 2006;163(2):210–216. doi:10.1176/appi.ajp.163.2.210.