Efficacy of Lurasidone in treatment of MDD-MF

MedicalResearch.com Interview with:
Antony Loebel, M.D. Executive Vice President and Chief Medical Officer, Sunovion, Head of Global Clinical Development for Sumitomo Dainippon Pharma GroupAntony Loebel, M.D.
Executive Vice President and Chief Medical Officer
Head of Global Clinical Development
Sumitomo Dainippon Pharma Group

MedicalResearch.com: What is the background for this study?

Response: Early predictors of subsequent clinical response are important in the treatment of depression, since 6-10 weeks of treatment are often required before full antidepressant response may occur. Early identification of patients who are unlikely to eventually achieve a response permits clinicians to intervene early to adjust the dose of medication, or switch to an alternative therapy.

Multiple studies in major depressive disorder (MDD, unipolar) have reported that early improvement at 2 weeks is significantly predictive of treatment response at 6-8 weeks.The most common early improvement criterion is a 20-25% reduction in the Hamilton Depression Rating Scale (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS) scores1-6.

Major depressive disorder with mixed features (MDD-MF) has recently been recognized as a diagnostic subtype in DSM-5. No research we are aware of has examined the predictive value of early improvement in patients diagnosed with MDD-MF.

The aim of the current post-hoc analysis was to evaluate the value of early improvement in the MADRS or the Clinical Global Impressions, Severity (CGI-S) scale as predictors of response to lurasidone in patients with MDD-MF.

MedicalResearch.com: What are the main findings?

Response: In patients treated with lurasidone for major depressive disorder with mixed features, early improvement at Weeks 2 or 3 was found to be a good predictor of clinical response at Week 6 endpoint (PPV in the range of 76-83%.

Lack of improvement by Week 3 was not found to be a good predictor of endpoint non-response.
The low NPV at Week 2 (42-45%) and Week 3 (55-58%) indicates that a large proportion of patients who did not achieve early improvement nonetheless went on to become responders by Week 6.

The results of the current analysis are in contrast to findings reported for antidepressants in acute treatment studies of major depression (non-mixed), where NPV values are typically in the range of 60-85%,1-6 and where less than 20% of patients without early improvement go on to become responders at Week 6.

MedicalResearch.com: What should readers take away from your report?

Response: A substantial proportion of patients with MDD-MF demonstrated clinically meaningful improvement in depression symptoms with lurasidone treatment, flexibly dosed at 20-60mg/d, within a time frame (3 weeks) that is commonly utilized for initial medication follow-up in clinical practice.

A large majority of patients who had early improvement at week 2 (76-83%) or week 3 (76-78%) continued to improve on lurasidone treatment and achieved responder status at the end of 6 weeks. This result supports a clinical decision to keep patients on lurasidone if there is discernable meaningful improvement within 3 weeks, even if patients haven’t yet fully responded.

Notably, however, even patients who did not demonstrate early improvement by week 3 had a good chance (42-45%) of ultimately responding to lurasidone 20-60mg/d by the end of week 6. This result suggests that keeping patients on flexible-dose lurasidone treatment for up to 6 weeks, which is commonly accepted as the duration of an adequate medication trial, may be appropriate before determining whether an alternative course of treatment is necessary.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This poster summarizes a post-hoc analysis of data from what is currently the only large placebo-controlled pharmacologic treatment study specifically in the MDD-MF patient population. Additional research is needed in order to better characterize these patients and to understand if/how patients with MDD-MF may differ from the general MDD (non-mixed features) population, particularly with respect to pharmacological treatment response.

Such research is needed, not only to support appropriate evidence-based treatment selection, but also to guide clinical decision-making after treatment is initiated.

MedicalResearch.com: Is there anything else you would like to add?

Response: Subthreshold hypomanic symptoms (or mixed features) is common in individuals with MDD. This form of depression is associated with increased risk for recurrence, suicide attempt, substance abuse, and functional disability. Patients with mixed depression generally have poorer outcomes and increased risk of hypomanic switch, when treated with standard antidepressants. Lurasidone, an atypical antipsychotic, has been found to be an efficacious and well-tolerated treatment in a randomized controlled trial in this population.


2016 European College of Neuropsychopharmacology abstract:

Efficacy of Lurasidone in the Treatment of MDD with Mixed Features: Early Improvement as a Predictor of Short-Term Response

Poster P.2.b.037: Lurasidone for MDD with Mixed Features: Effect of Baseline Depression Severity on Clinical Outcome (Monday, September 19, 2016
Authors: J. Craig Nelson, Joyce Tsai, Andrei Pikalov, Yongcai Mao, Josephine Cucchiaro, Antony Loebel

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

[wysija_form id=”5″]

Last Updated on October 9, 2016 by Marie Benz MD FAAD