Lurasidone for Cognitive Improvement in Bipolar Disorder

(ELICE_BD Trial)

No longer recruiting at 8 trial locations

Overseen By Keming Gao, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Lakshmi N Yatham

Must be taking: Mood stabilizers, Atypical antipsychotics

Must not be taking: Procognitive, Clozapine, Tricyclics, Anticholinergics

Disqualifiers: Unstable medical illnesses, Anxiety, ADHD, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether lurasidone, an antipsychotic medication, can improve thinking skills in people with bipolar disorder, a condition causing extreme mood swings, who are stable but experiencing cognitive difficulties. Participants will receive either lurasidone or a placebo in addition to their current treatment for six weeks. Individuals with bipolar disorder and cognitive issues who are on a stable treatment plan might be suitable for this study. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants a chance to contribute to the advancement of treatment options.

Do I have to stop taking my current medications for the trial?

The trial requires that you stay on your current mood stabilizer or atypical antipsychotic at a stable dose for two weeks before randomization. However, you cannot take certain medications like procognitive drugs, clozapine, tricyclic antidepressants, or strong CYP3A4 inhibitors and inducers.

Will I have to stop taking my current medications?

The trial requires that you continue taking your current mood stabilizer or atypical antipsychotic at a stable dose for at least two weeks before starting the study. However, certain medications like procognitive drugs, clozapine, and some others are not allowed.

Is there any evidence suggesting that lurasidone is likely to be safe for humans?

Research has shown that lurasidone is generally safe and well-tolerated for people with bipolar depression. In a study lasting up to two years, young patients using lurasidone reported few side effects. Another study found that only about 23% of patients stopped using lurasidone, suggesting it was easy to continue taking. Additionally, only 37% experienced minor side effects.

The FDA has already approved lurasidone for treating bipolar depression in adults, providing extra reassurance about its safety. While the current trial focuses on improving thinking skills, the safety information from these other studies remains useful. Lurasidone has been studied extensively, and most people handle it well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar disorder?

Unlike the standard treatments for bipolar disorder, which often focus on mood stabilization, lurasidone is being explored for its potential to improve cognitive function. Researchers are excited about lurasidone because it targets the serotonin 5-HT7 receptor, which is thought to play a role in cognition. This unique mechanism of action sets it apart from typical mood stabilizers and antipsychotics, offering hope for enhancing cognitive clarity in individuals with bipolar disorder.

What evidence suggests that lurasidone might be an effective treatment for cognitive impairment in bipolar disorder?

Research has shown that lurasidone can improve thinking and memory in people with bipolar disorder. In this trial, participants will receive either lurasidone or a placebo alongside their current treatment for six weeks. For treating depression symptoms, the most effective results with lurasidone occur at daily doses of 40 to 60 mg. Some studies suggest that individuals with bipolar depression may begin to feel better after just two weeks of taking lurasidone. Additionally, research has found that those taking lurasidone think more clearly than those on a placebo or other treatments over six months. These findings suggest that lurasidone might help with thinking and memory problems in people with bipolar disorder. ^{2 6 7 8 9}

Who Is on the Research Team?

Lakshmi N Yatham, MBBS,MRCPsy

Principal Investigator

University of British Columbia, Department of Psychiatry

Are You a Good Fit for This Trial?

Adults aged 19-65 with Bipolar I or II Disorder in remission, who are on stable mood stabilizers or antipsychotics, and show cognitive impairment. They must understand English or Japanese, have an IQ over 80, and not be at risk of self-harm. Women must use effective contraception or be postmenopausal.

Inclusion Criteria

MADRS and YMRS score less than or equal to 8

Patients who show cognitive impairments on specified tests at screening visit

WAIS-IV vocabulary scaled score >5

Exclusion Criteria

Current criteria for anxiety disorder, ADHD, or other learning disorders

Diagnosis of alcohol/substance abuse or dependence within the past month

Significant risk of harm to self or others

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either lurasidone or placebo adjunctive therapy for 6 weeks

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lurasidone
• Placebo

Trial Overview The study is testing if Lurasidone improves thinking abilities in bipolar patients compared to a placebo. Participants will either receive Lurasidone or a dummy pill for six weeks while their cognitive functions are monitored.

How Is the Trial Designed?

Group I: Lurasidone Experimental Treatment 1 Intervention

Lurasidone 20 - 80 mg / day added to current treatment for 6 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo added to current treatment for 6 weeks

Who Is Running the Clinical Trial?

Lakshmi N Yatham

Lead Sponsor

Trials

2

Recruited

100+

Nazlin Walji

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

Lurasidone is a newly approved antipsychotic for children, showing efficacy in treating schizophrenia and bipolar disorder, with a favorable safety and tolerability profile for long-term use.

The drug has also been explored for off-label uses in childhood conditions such as autism spectrum disorders and Tourette's syndrome, demonstrating effectiveness across various psychopathological symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Using Lurasidone in the treatment of mental illness in childhood]. Goryunov, AV.[2022]

In a six-week randomized, double-blind trial involving 76 patients with Bipolar I or II, Lurasidone demonstrated a significantly better response rate (66%) in reducing symptoms compared to placebo (42%).

The study indicated that Lurasidone is effective in improving overall health and managing bipolar symptoms, with patients tolerating the drug well and showing no significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TULIP study: Trail of Lurasidone in bipolar disorder in Pakistan. Khan, N., Nasar, A., Bajwa, S., et al.[2022]

In a pilot study involving 34 euthymic bipolar I disorder patients, lurasidone adjunctive therapy significantly improved global cognition scores compared to treatment as usual (TAU), with a moderate to large effect size of 0.82.

While lurasidone showed promising cognitive benefits, it also had a higher incidence of adverse events (60% in the lurasidone group vs. 13% in TAU), indicating the need for careful monitoring in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurasidone versus treatment as usual for cognitive impairment in euthymic patients with bipolar I disorder: a randomised, open-label, pilot study. Yatham, LN., Mackala, S., Basivireddy, J., et al.[2019]

Lurasidone is an atypical antipsychotic approved for treating bipolar depression, showing greater efficacy than placebo when used alone or with lithium or valproate, based on clinical trials.

It has a favorable safety profile, with minimal weight gain and no significant changes in glucose, lipids, or heart rhythm, making it a promising option for managing depressive episodes in bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of lurasidone as an adjunct to lithium or divalproex in the treatment of bipolar disorder. Alamo, C., López-Muñoz, F., García-García, P.[2015]

In a cost-effectiveness analysis over a 3-month period involving patients with bipolar depression, lurasidone was found to achieve a higher remission rate (52.0%) compared to quetiapine XR (43.2%), indicating it may be more effective in treating this condition.

Despite slightly higher total costs for lurasidone ($4982 vs $4676), it demonstrated a favorable incremental cost-effectiveness ratio of $3474 per remission, with an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression. Rajagopalan, K., Meyer, K., O'Day, K., et al.[2015]

A 6-month treatment with lurasidone in older adults with bipolar I depression showed significant improvement in depressive symptoms, with mean reductions in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores of -6.2 for monotherapy and -6.7 for adjunctive therapy.

Lurasidone treatment was well tolerated, with minimal impact on weight and metabolic parameters, and low rates of switching to hypomania or mania, indicating its safety for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Long-Term Treatment with Lurasidone in Older Adults with Bipolar Depression: Post-Hoc Analysis of a 6-Month, Open-Label Study. Forester, BP., Sajatovic, M., Tsai, J., et al.[2019]

In a study of 61 bipolar disorder patients, lurasidone was found to significantly reduce syndromal depression rates by nearly half and increase euthymia rates, suggesting its effectiveness as an adjunctive treatment.

However, 54.1% of patients discontinued lurasidone primarily due to adverse events like akathisia and weight gain, indicating challenges with tolerability in this population already on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer-Term Effectiveness and Tolerability of Adjunctive Open Lurasidone in Patients With Bipolar Disorder. Miller, S., Do, D., Gershon, A., et al.[2019]

Lurasidone monotherapy significantly improved depressive symptoms in patients with non-rapid cycling bipolar depression compared to placebo, with effect sizes of 0.47 and 0.41 for the 20-60 mg/day and 80-120 mg/day doses, respectively.

In patients with rapid cycling bipolar depression, while lurasidone showed some reduction in depressive symptoms, the improvement was not statistically significant, likely due to a small sample size and high placebo response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of lurasidone in bipolar I depression with and without rapid cycling: A pooled post-hoc analysis of two randomized, placebo-controlled trials. Kato, M., Masuda, T., Sano, F., et al.[2023]

Lurasidone significantly reduced depressive symptoms in adults with bipolar I disorder, achieving over a 50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared to placebo in two 6-week trials, with a low number needed to treat of ≤7 for an additional response.

The medication has a favorable safety profile, with lower risks of weight gain and metabolic disturbances compared to other antipsychotics, although common side effects included akathisia and extrapyramidal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurasidone: a review of its use in adult patients with bipolar I depression. Sanford, M., Dhillon, S.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11574478/

Efficacy and acceptability of lurasidone for bipolar depression For depressive symptoms, lurasidone achieved the best improvement effect in the range of 40–60 mg and reached the peak effect at 50 mg (SMD − ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725003660

Real-world Effectiveness and Tolerability of Lurasidone in ... LUR significantly improved depressive symptoms in patients with BD2 at 8 W. Moreover, treatment with LUR resulted in early improvement at 2 W and efficacy for ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02731612

NCT02731612 | Study of the Efficacy of Lurasidone in ... Improvement in cognitive performance in Euthymic bipolar patients treated with Lurasidone vs Placebo adjunctive therapy. Cognitive improvement will be measured ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39557452/

Efficacy and acceptability of lurasidone for bipolar depression Conclusions: A daily dose of 40-60 mg of lurasidone is a reasonable choice for bipolar depression treatment. Trial registration number: ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2215036617300469

Articles Lurasidone versus treatment as usual for cognitive ... Furthermore, at 6 months, patients who had received lurasidone 40–160 mg daily performed better than did both placebo and quetiapine extended release groups.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8568779/

Tolerability, Safety, and Effectiveness of Two Years ... Up to 2 years of treatment with lurasidone in youth presenting with bipolar depression was generally safe and well tolerated, with a relatively low rate of ...

7. mentalhealth.bmj.com mentalhealth.bmj.com/content/27/1/e301165

Efficacy and acceptability of lurasidone for bipolar depression In terms of efficacy, a daily dose of 40–60 mg showed optimal effects in improving depressive and anxiety symptoms, CGI score and disability.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29146409/

Post-Hoc Analysis of a 6-Month, Open-Label Study Patients treated with 6 months of lurasidone showed a mean improvement on the MADRS in both the monotherapy (-6.2) and adjunctive therapy (-6.7) groups.

9. fda.gov fda.gov/media/187200/download?attachment

Pediatric Postmarketing Pharmacovigilance Review The safety and effectiveness of LATUDA has not been established in pediatric patients less than 10 years of age with bipolar depression.