The effectiveness of lurasidone as an adjunct to lithium or divalproex in the treatment of bipolar disorder

Abstract

The majority of patients with bipolar disorder spend a lot of time in depressive episodes that impose a great burden on patients, caregivers, and society and accounts for the largest part of the morbidity-mortality of the illness. Lurasidone is an atypical antipsychotic with a potent binding affinity as antagonist for D₂, 5-HT_2A, 5-HT₇, and partial agonist at 5-HT_1A receptors. Affinity for other receptors as H₁ and muscarinic were negligible. Lurasidone was approved in 2010 for the treatment of schizophrenia and recently, 2013, for bipolar depression in monotherapy and an adjunct to lithium or valproate. Clinical trials have established that lurasidone adjuvant to lithium or valproate has more efficacy than the placebo and is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, or the QT interval. Additional studies are desirable to know the clinical profile of lurasidone in long-term treatment, in patients with bipolar II disorders, and versus other antipsychotic agents.

Keywords::

• adjunctive therapy
• atypical antipsychotics
• bipolar disorder
• lithium
• lurasidone
• valproate

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Bipolar disorder (BD) is a complex and chronic psychiatric condition with a lifetime prevalence of 3%.

• Depressive episodes of BD are associated with greater impairment in work, family and social life than episodes of mania. The lifetime risk for suicide attempts and completed suicide in BD is one of the highest amongst psychiatric illnesses.

• Delays in recognizing and diagnosing bipolar depression can hinder appropriate treatment.

• The pharmacological treatment of BD, including antipsychotics, anticonvulsants or lithium, has grown substantially.

• Antidepressants are the most frequently prescribed drugs, but recommendations from evidence-based guidelines are not conclusive and do not overtly support their use.

• Anticonvulsants have been used classically in the treatment of BD, but its efficacy in bipolar depression is at least controversial, except lamotrigine (prevention of relapse of bipolar depression).

• Among antipsychotic drugs, only quetiapine and olanzapine, especially associated with fluoxetine, have demonstrated significant improvement in patients with bipolar depression.

• Lurasidone is an atypical antipsychotic agent that was originally approved in 2010 by the US FDA for the treatment of patients with schizophrenia.

• Lurasidone is the first atypical antipsychotic to receive FDA approval as both monotherapy and adjunctive therapy with lithium or valproate for the treatment of bipolar depression.

• The antidepressant effect of lurasidone could be due to the differential receptorial profile. The mechanism of antidepressant and anxiolytic effect of lurasidone is unknown, but we can postulate that 5-HT_1A and 5-HT₇ receptors are implicated.

• Lurasidone shows, in bipolar patients, significantly more improvement in depression than in the placebo-treated patients.

• The efficacy of lurasidone, as an adjunctive therapy with lithium or valproate, was established in a 6-week, multicenter, randomized, double-blind, placebo-controlled study of adult patients who met the DSM-IV-TR criteria for major depressive episodes associated with bipolar I disorder, with or without rapid cycling, and without psychotic features.

• In patients with bipolar depression, lurasidone added to stable doses of lithium or valproate significantly improved depressive symptoms and associated anxiety symptoms, as well as assessments of quality of life and functioning.

• In adjunctive therapy, lurasidone was associated with minimal effect on weight, lipids and measures of glycemic control.

Notes