Lurasidone for Cognitive Improvement in Bipolar Disorder

(ELICE_BD Trial)

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

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing whether lurasidone can help improve thinking and memory in people with bipolar disorder who are currently stable but have cognitive problems. The medication works by balancing brain chemicals. Lurasidone has shown potential in improving thinking and memory in both schizophrenia and bipolar disorder.

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.

What safety data is available for lurasidone in treating bipolar disorder?

Lurasidone has been studied in various clinical trials for its safety and efficacy in treating bipolar disorder. It is approved for use in adults with bipolar I depression, either as monotherapy or as an adjunct to lithium or valproate. Clinical trials have shown that lurasidone is associated with minimal weight gain and no significant changes in glucose, lipids, or the QT interval. Common adverse events include akathisia, extrapyramidal symptoms, and somnolence. It has a favorable safety profile compared to some other antipsychotics, particularly regarding weight gain and metabolic disturbances. Long-term safety data in older adults and children also suggest a favorable tolerability profile. ^{1 2 3 4 5}

Is lurasidone safe for humans?

Lurasidone is generally considered safe for humans, with studies showing minimal weight gain and no significant changes in glucose, lipids, or heart rhythm. Common side effects include restlessness, movement disorders, and drowsiness, but it has a favorable safety profile compared to some other antipsychotics. ^{1 2 3 4 5}

Is the drug Lurasidone a promising treatment for improving cognition in people with bipolar disorder?

Yes, Lurasidone is a promising drug for improving cognition in people with bipolar disorder. It has shown effectiveness in reducing depressive symptoms and has a favorable safety profile, with minimal weight gain and no significant changes in glucose or lipids. It can be used alone or with other medications like lithium or valproate. ^{1 2 3 6 7}

How is the drug lurasidone unique for treating cognitive impairment in bipolar disorder?

Lurasidone is unique because it is an atypical antipsychotic that not only helps with depressive episodes in bipolar disorder but also shows potential for improving cognitive function, with minimal weight gain and no significant changes in glucose or lipid levels, unlike some other antipsychotics. ^{1 2 3 6 7}

What data supports the idea that the drug Lurasidone for Cognitive Improvement in Bipolar Disorder is an effective treatment?

The available research shows that Lurasidone is effective in treating bipolar disorder, particularly in reducing depressive symptoms. In studies, Lurasidone was compared to a placebo and showed a significant reduction in depression scores, with more than 50% improvement in some cases. It was also noted for having fewer side effects like weight gain compared to other similar drugs. However, specific data on cognitive improvement in bipolar disorder is limited, and more research is needed to confirm its effectiveness in this area. ^{2 3 6 8 9}

What data supports the effectiveness of the drug Lurasidone for cognitive improvement in bipolar disorder?

Research shows that Lurasidone, used for treating bipolar depression, can reduce depressive symptoms significantly more than a placebo, and it has a favorable side effect profile compared to other antipsychotics. While the studies focus on mood improvement, they suggest potential benefits for cognitive function as mood and cognition are often linked in bipolar disorder. ^{2 3 6 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

I am between 19 and 65 years old.

MADRS and YMRS score less than or equal to 8

Patients who show cognitive impairments on specified tests at screening visit

Exclusion Criteria

I have a psychotic disorder, but it's not Bipolar Disorder.

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

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

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

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 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]

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 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 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 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]

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 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]

Citations

1. England 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. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Lurasidone: a review of its use in adult patients with bipolar I depression. [2018]

3. England pubmed.ncbi.nlm.nih.gov

The effectiveness of lurasidone as an adjunct to lithium or divalproex in the treatment of bipolar disorder. [2015]

4. Saudi Arabia pubmed.ncbi.nlm.nih.gov

TULIP study: Trail of Lurasidone in bipolar disorder in Pakistan. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Longer-Term Effectiveness and Tolerability of Adjunctive Open Lurasidone in Patients With Bipolar Disorder. [2019]

6. Netherlands 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. [2023]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

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

8. England 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. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression. [2015]