Lurasidone adjunctive with lithium or valproate for bipolar depression: A placebo-controlled trial utilizing prospective and retrospective enrolment cohorts

Abstract

In this study, designed to evaluate the efficacy of lurasidone as adjunctive therapy with lithium or valproate, patients with bipolar I depression were randomized to 6 weeks of double-blind treatment with lurasidone (N = 180) or placebo (N = 176), added to background treatment with lithium or valproate. All patients were treated with lithium or valproate for a minimum of 4 weeks prior to screening. This was confirmed either by prospective treatment after study enrolment (run-in cohort), or retrospectively, with blood levels of lithium and valproate at screening (non-run-in cohort). Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP-S), respectively. Treatment with lurasidone was associated with non-significant improvement at week 6 vs. placebo for the MADRS total score (-11.8 vs -10.4; P = 0.176), and the CGI-BP-S score (-1.36 vs -1.13; P = 0.095). Significant separation from placebo was observed from weeks 2-5 for the MADRS and weeks 3-5 for the CGI-BP-S. Improvement in the placebo-subtracted MADRS total score was notably larger at week 6 for the non-run-in cohort compared to the run-in cohort (LS mean difference in endpoint change scores, -4.6; P = 0.009). Adverse events most frequently reported for lurasidone were akathisia, somnolence, and extrapyramidal side effects. In conclusion, lurasidone adjunctive with lithium or valproate demonstrated significant improvement in depressive symptoms based on the MADRS from weeks 2-5 but not at the primary week 6 endpoint.

Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study

“…[19][20][21][22][23][24][25][26][27][28][29][30] Notably, treatment with lurasidone has previously demonstrated significant anxiolytic treatment effects in three separate 6-week trials in bipolar depression. [33][34][35] While further studies are necessary to confirm these findings, the results of the current analysis, taken together with the consistent improvements in HAM-A scores observed in prior bipolar depression studies, suggest that lurasidone may be a useful treatment for mixed forms of major depression associated with anxiety.…”

“…32 Treatment with lurasidone was associated with significant improvement in anxiety symptoms compared with placebo in patients with bipolar depression. [33][34][35] The purpose of the present post-hoc analysis was to assess the efficacy of lurasidone in treating MDD patients with mixed features who present with moderate-to-severe levels of anxiety.…”

Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta‐analysis of randomized controlled trials

“…[1][2][3][4][5] What magnifies this depressive-predominant disability is the modicum of drugs with regulatory approval specifically for bipolar depression. In the US, the following drugs have been approved by the Food and Drug Administration (FDA) for treating bipolar depression: [olanzapine/ fluoxetine combination (2003), 6 quetiapine (2006) 7,8 lurasidone (2013), 9,10 and cariprazine (2019) 11 ]. This contrasts, over the same time course of drug development remarkably with the 7, 11, and 20 treatments, respectively, in acute mania, schizophrenia, and major depression.…”

The Treatment of Bipolar Depression: Current Status and Future Perspectives

“…Evidence to support efficacy of lurasidone in the treatment of bipolar depression comes from three large placebo-controlled studies [51][52][53]. In the first, comparing lurasidone monotherapy versus placebo in bipolar I depression over a 6-week period, lurasidone significantly reduced depressive symptoms compared with placebo [51].…”