Lurasidone HCl tablets have been approved for adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate. The drug, an atypical antipsychotic, was already indicated for schizophrenia.
Lurasidone's efficacy was established in a 6-week monotherapy trial and a 6-week adjunctive therapy study with lithium or valproate.
In the multicenter monotherapy trial, 505 adult patients with major depressive episodes associated with bipolar I disorder were randomly assigned to 1 of 2 flexible-dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d) or placebo. The mean daily dose was 31.8 mg in the 20- to 60-mg group and 82.0 mg in the higher dose group. In both dosage groups, nearly all patients were titrated to a higher dose during the study. Eight percent to 19% of patients in each of the 3 groups reported as-needed treatment with lorazepam or zolpidem.
Lurasidone was superior to placebo in reducing depressive symptoms and lowering disease-severity scores. There was a statistically significant reduction from baseline to week 6 in core depression symptoms for both dosages (P < .001), but the higher dose range did not provide additional efficacy. The proportion of patients in remission at endpoint was significantly greater in the 2 drug groups (42% and 40%), compared with patients on placebo (25%). Both dosages also significantly improved anxiety symptoms.
Lurasidone has been extensively studied for its use in treating schizophrenia; the monotherapy trial revealed no new safety concerns or risks, the researchers say. Adverse events (AEs) were mostly mild or moderate. Researchers found a modest, dose-related increase in the frequency of nausea, sedation, vomiting, and extrapyramidal symptoms for the higher dose range. Similar numbers of patients withdrew from each group.
In a second multicenter double-blind study, 348 patients who were still symptomatic after treatment with lithium or valproate were randomly assigned to flexibly dosed lurasidone 20 mg/d to 120 mg/d or placebo. In this study, too, patients in the treatment groups showed significantly greater improvement in depressive symptoms, associated anxiety symptoms, and quality of life and functioning.
The researchers say this is, to their knowledge, the first large-scale, randomized, placebo-controlled trial to demonstrate efficacy of any medication adjunctive to mood stabilizers for the acute treatment of bipolar depression. “In particular,” they say, “no positive controlled studies have been published to date regarding the use of atypical antipsychotic medications as adjunctive therapy for patients with bipolar depression.”
Lurasidone’s effectiveness beyond 6 weeks has not been established in controlled studies. The manufacturer advises periodically reevaluating the long-term usefulness of the drug for the individual patient. As with other antidepressants, there is an increased risk of suicidal thoughts or actions. Lurasidone may cause serious AEs, including increased risk of death in elderly people who are confused or have memory loss. It is not intended for treatment of dementia-related psychosis.
Lurasidone is known to have a small dose-related effect on prolactin, as well as weight, lipids, and measures of glycemic control. However, it has appreciably fewer weight and metabolic effects, compared with other atypical antipsychotic agents, the researchers note. The metabolic profile of lurasidone in the adjunctive-therapy trial, the researchers say, suggests that it may be “associated with low cardiometabolic risk in this vulnerable clinical population.”
Sources
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):160-168.
doi: 10.1176/appi.ajp.2013.13070984.
Loebel A, Cucchiaro J, Silva R, et al. Am J Psychiatry. 2014;171(2):169-177.
doi: 10.1176/appi.ajp.2013.13070985.