Depression in
bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the
neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, depressed mood state, were randomized to
pregnenolone (titrated to 500 mg/day) or placebo, as add-on
therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young
Mania Rating Scale (YMRS). Serum
neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed. Depression remission rates were greater in the
pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ(2)(1)=3.99, p=0.046), but not the HRSD. Large baseline-to-exit changes in
neurosteroid levels were observed in the
pregnenolone group but not in the placebo group. In the
pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in
allopregnanolone (r(22)=-0.43, p=0.036) and
pregNANolone (r(22)=-0.48, p=0.019) levels.
Pregnenolone was well tolerated. The results suggest that
pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered.