MYDAYIS® for Bipolar Depression

No longer recruiting at 1 trial location

Overseen By Susan L McElroy, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Mood stabilizers, Antipsychotics

Must not be taking: MAOIs

Disqualifiers: Suicidality, Substance abuse, Psychosis, Cardiovascular problems, others

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

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

Compensation: Varies

Number of Visits: 10

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of MYDAYIS® (amphetamine/dextroamphetamine) as an add-on treatment for adults with bipolar depression. Participants will receive either MYDAYIS® or a placebo (a pill with no active drug) to assess its impact on depression symptoms. It is suitable for individuals with bipolar I or II who are currently experiencing a major depressive episode that hasn't improved with their current medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that you must not be on monoamine oxidase inhibitors (MAOIs) or have used them within the last 14 days. You can continue with stable anti-manic mood stabilizers, antipsychotic therapy, and behavioral treatments.

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

Research has shown that MYDAYIS® is generally safe for certain conditions. The FDA has approved it for treating ADHD (Attention Deficit Hyperactivity Disorder), indicating a well-understood safety profile. In previous studies, participants took doses similar to those planned for this trial, ranging from 12.5 mg to 50 mg per day, and most handled these doses well.

However, MYDAYIS® carries some risks. As a brain stimulant, it can cause side effects like a faster heartbeat or anxiety. There is also a chance it could be habit-forming for some individuals.

While the safety information is encouraging, this study tests MYDAYIS® for a new purpose—treating bipolar depression. Even with a good safety record for other uses, it remains important to assess its effectiveness and safety in this specific context. ^{1 2 3 4 5}

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

Researchers are excited about MYDAYIS® for bipolar depression because it offers a potentially faster-acting and more precise treatment option. Unlike traditional treatments like mood stabilizers and antipsychotics, which can take weeks to show effects, MYDAYIS® is an extended-release formulation that might provide quicker symptom relief. Additionally, MYDAYIS® is designed to improve focus and energy levels, which are often problematic in bipolar depression. This unique approach targets the neurotransmitter systems in a way that could offer more balanced mood control with fewer side effects.

What evidence suggests that MYDAYIS® might be an effective treatment for bipolar depression?

Research has shown that MYDAYIS®, a type of stimulant medication, might help improve symptoms of bipolar depression when combined with other treatments. In this trial, some participants will receive MYDAYIS® to evaluate its effectiveness. A study on a similar stimulant, lisdexamfetamine, found that it reduced depressive symptoms in people with bipolar depression, suggesting that MYDAYIS® might work similarly. Although direct evidence for MYDAYIS® in treating bipolar depression is limited, its mechanism is promising. It affects brain chemicals that send signals, potentially improving mood and focus. Further research is underway to confirm these effects. ^{2 4 6 7 8}

Who Is on the Research Team?

Mark A Frye

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults aged 18-55 with Bipolar I or II disorder, currently having a major depressive episode despite stable mood stabilizer or antipsychotic therapy. They can have attention deficit or binge eating disorders and continue behavioral treatments. Excluded are those with certain mania scores, MAOI use, drug abuse history, significant heart issues, pregnancy without contraception use, recent suicidality attempts or ideation.

Inclusion Criteria

Bipolar I or II disorder as confirmed by structured diagnostic interview by Axis I of the SCID by DSM-IV-TR

Patients who have both attention deficit disorder and binge eating disorder will be allowed to participate.

You can continue with therapy focused on your main diagnosis, like cognitive-behavioral therapy (CBT).

Exclusion Criteria

Baseline Young Mania Rating Scale (YMRS) score ≥ 8

Concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a monoamine oxidase inhibitor

Known lifetime history of DSM-IV-TR diagnosis of cocaine or methamphetamine abuse or dependence. Nicotine dependence will be an exception

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MYDAYIS® or placebo as adjunctive therapy for bipolar depression, with dose escalation over 8 weeks

8 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MYDAYIS®
• Placebo

Trial Overview The study is testing MYDAYIS Extended-Release Capsules as an additional treatment for bipolar depression in adults. Participants will either receive the actual medication or a placebo over an 8-week period at multiple sites to assess its safety and effectiveness.

How Is the Trial Designed?

Group I: Mydayis - Active Active Control 1 Intervention

MYDAYIS®, Oral administration, dose regimen for Double blind phase and open label phase. 12.5 mg x 7 days. 25 mg x 7 days 37.5 mg x 14 days 50 mg daily x 28 days

Group II: Placebo Placebo Group 1 Intervention

Matching placebo, Oral administration, dose regimen for Double blind phase and open label phase. 12.5 mg x 7 days. 25 mg x 7 days 37.5 mg x 14 days 50 mg daily x 28 days

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Lindner Center of HOPE

Collaborator

Trials

29

Recruited

1,400+

Published Research Related to This Trial

In a 2-week placebo-controlled trial involving 23 men with HIV, 73% of those treated with dextroamphetamine reported significant improvements in mood and energy, compared to only 25% in the placebo group, indicating its efficacy as a treatment for depression and fatigue.

The study found no evidence of tolerance, abuse, or dependence on dextroamphetamine, suggesting it is a safe option for patients with HIV experiencing depressive symptoms and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial. Wagner, GJ., Rabkin, R.[2019]

In a study involving 29 patients, intravenous S-adenosyl methionine (SAM) treatment led to a significant mood elevation in 9 out of 11 bipolar patients, indicating its potential efficacy in treating bipolar depression.

The study also found that 38% of trials resulted in a switch from depression to elation, suggesting that SAM may influence mood states, particularly in bipolar patients, while no significant response was observed in unipolar patients or those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The switch mechanism and the bipolar/unipolar dichotomy. Carney, MW., Chary, TK., Bottiglieri, T., et al.[2019]

In two 8-week studies involving 561 outpatients with bipolar I disorder, aripiprazole did not show significant improvement over placebo in reducing depressive symptoms by Week 8, despite some early benefits observed in the first six weeks.

Patients taking aripiprazole experienced more side effects, such as akathisia and insomnia, and had higher discontinuation rates compared to those on placebo, indicating potential safety concerns with its use for bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. Thase, ME., Jonas, A., Khan, A., et al.[2015]

In a 6-week open trial involving 24 AIDS patients with depression and low energy, 95% of those who completed the treatment reported significant improvements in mood and energy when treated with dextroamphetamine at a median dose of 10 mg/day.

The findings suggest that dextroamphetamine may serve as a fast-acting antidepressant option for individuals with late-stage HIV, highlighting the need for further controlled studies to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextroamphetamine as a treatment for depression and low energy in AIDS patients: a pilot study. Wagner, GJ., Rabkin, JG., Rabkin, R.[2019]

In a study involving 16 healthy volunteers, the administration of 20 mg D-amphetamine produced expected subjective and cardiovascular changes, suggesting it can mimic some aspects of mania.

However, the subacute administration of lithium (1200 mg for 7 days) did not reduce these effects, indicating that D-amphetamine's mechanism of action may differ from that of mania, thus questioning the validity of using this model to study manic episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium does not attenuate the effects of D-amphetamine in healthy volunteers. Silverstone, PH., Pukhovsky, A., Rotzinger, S.[2019]

Bipolar disorder is characterized by more time spent in depressive episodes than in elevated mood states, leading to significant morbidity and mortality, which highlights the need for effective treatment strategies.

While antidepressants are commonly prescribed, their use in bipolar depression is controversial; fluoxetine combined with olanzapine has the strongest evidence, but long-term maintenance treatment typically relies on mood stabilizers like lithium and lamotrigine instead.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological management of bipolar depression: acute treatment, maintenance, and prophylaxis. Vieta, E., Valentí, M.[2021]

In a study of 25 outpatients with bipolar depression, lisdexamfetamine (LDX) showed a greater improvement in self-reported depressive symptoms and daytime sleepiness compared to placebo, despite similar overall rates of improvement in depressive symptoms as measured by the Montgomery-Asberg Depression Scale.

LDX was well tolerated with no serious adverse events reported, but the study's small sample size may limit the findings, suggesting that further research with larger groups is needed to fully understand the efficacy of psychostimulants in treating bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive lisdexamfetamine in bipolar depression: a preliminary randomized, placebo-controlled trial. McElroy, SL., Martens, BE., Mori, N., et al.[2015]

In a pooled analysis of 1214 patients from two studies, olanzapine monotherapy significantly reduced depression symptoms in bipolar I patients compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) over 6 weeks.

The presence of melancholic features at baseline was identified as a factor that could predict a better response to olanzapine treatment, highlighting the importance of patient characteristics in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of olanzapine monotherapy in acute bipolar depression: a pooled analysis of controlled studies. Tohen, M., Katagiri, H., Fujikoshi, S., et al.[2018]

In a 6-month open-label study involving 867 patients with bipolar I depression, adjunctive armodafinil (150-200 mg/day) was found to be generally safe and well tolerated, with common side effects including headache, insomnia, and anxiety, but no significant worsening of mania or suicidality.

The study suggested that armodafinil may improve depressive symptoms and patient functioning when used alongside standard mood stabilizers, indicating a potentially favorable risk profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of armodafinil in bipolar depression: A 6-month open-label extension study. Ketter, TA., Amchin, J., Frye, MA., et al.[2018]

The study reviews the placebo response rates in clinical trials for treating acute mania and bipolar depression, highlighting the importance of understanding these rates to improve trial design.

It discusses strategies to minimize placebo responses and suggests optimal trial durations, which are crucial for developing effective treatments for various age groups, including children and older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo effect in randomized, controlled studies of acute bipolar mania and depression. Keck, PE., Welge, JA., McElroy, SL., et al.[2019]

A brain-injured adolescent showed a lasting and unexpected reduction in manic symptoms after treatment with dextroamphetamine, despite having previously failed other standard treatments like divalproex and lithium.

This case suggests that stimulants like dextroamphetamine could be useful in predicting treatment responses for mania and may help in subclassifying bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case study: antimanic effectiveness of dextroamphetamine in a brain-injured adolescent. Max, JE., Richards, L., Hamdan-Allen, G.[2018]

Selective serotonin reuptake inhibitors (SSRIs) and lamotrigine are currently the most effective treatments for the depressed phase of bipolar disorder, based on a review of existing literature.

Combining an atypical antipsychotic with either an SSRI or lamotrigine may be a promising first-line treatment strategy, as it can minimize the risk of triggering mania when used alongside mood stabilizers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of acute treatments for bipolar depression. Silverstone, PH., Silverstone, T.[2019]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04235686/8-week-multi-site-study-of-mydayisr-for-bipolar-depression

8 Week Multi-site Study of MYDAYIS® for Bipolar Depression This protocol is a Phase 2 multi-site study which aims to evaluate the safety and effectiveness of MYDAYIS® as adjunctive therapy for adults ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20467509

8 Week Multi-site Study of MYDAYIS® for Bipolar Depression The purpose of this study is to assess the effectiveness and safety of MYDAYIS® as an augmentation agent for bipolar depression.

3. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT04235686/

Trial | NCT04235686 This protocol is a Phase 2 multi-site study which aims to evaluate the safety and effectiveness of MYDAYIS\® as adjunctive therapy for adults with bipolar ...

4. withpower.com withpower.com/trial/phase-3-bipolar-disorder-6-2020-a9d06

MYDAYIS® for Bipolar Depression · Info for Participants Additionally, a study on lisdexamfetamine, a similar stimulant, showed improvements in self-reported depressive symptoms in bipolar depression, indicating ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/75/NCT03945175/Prot_SAP_000.pdf

Study of the Duration and Efficacy of MYDAYIS on Adult ... A third purpose is extend the data on the effects of Mydayis on executive function to include neuropsychological measures of executive function ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/022063s000lbl.pdf

Mydayis - accessdata.fda.gov CNS stimulants, including MYDAYIS, other amphetamine - containing products, and methylphenidate, have a high potential for abuse and dependence (5.1, 9.3).

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK507808/

Dextroamphetamine-Amphetamine - StatPearls - NCBI - NIH Objectives: Identify the indications, contraindications, and potential adverse effects of dextroamphetamine-amphetamine, including risks for ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/022063s005lbl.pdf

Mydayis - accessdata.fda.gov The safety data for pediatric patients (13 to 17 years) is from 1 randomized, double-blind, placebo- controlled study of doses of 12.5 mg to 25 mg. The ...