MYDAYIS® for Bipolar Depression

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

90 Participants Needed

Trial Summary

What is the purpose of this trial?

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 depression. Results from this study WILL NOT be used to contribute to an approval of MYDAYIS \® for this indication.

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 that the drug MYDAYIS® could be effective for treating bipolar depression?

There is some evidence suggesting that dextroamphetamine, a component of MYDAYIS®, may have antimanic effects, as seen in a case study of a brain-injured adolescent. Additionally, a study on lisdexamfetamine, a similar stimulant, showed improvements in self-reported depressive symptoms in bipolar depression, indicating potential benefits of stimulant medications in this condition. ^{1 2 3 4 5}

Is MYDAYIS® (amphetamine/dextroamphetamine) safe for humans?

The research does not provide specific safety data for MYDAYIS® (amphetamine/dextroamphetamine) in humans, but a related study on lisdexamfetamine, another stimulant, found it was well tolerated without serious adverse events, though there was one case of suspected misuse. ^{2 6 7 8 9}

How does the drug MYDAYIS® differ from other treatments for bipolar depression?

MYDAYIS® is unique because it contains dextroamphetamine, which has shown potential for rapid mood improvement and increased energy in other conditions like HIV-related depression. This fast-acting property may offer a novel approach compared to traditional bipolar depression treatments, which often involve mood stabilizers and atypical antipsychotics. ^{4 7 10 11 12}

Research Team

Mark A Frye

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

Male or female between 18 and 55 years of age

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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-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]

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 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]

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 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]

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]

References

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

Case study: antimanic effectiveness of dextroamphetamine in a brain-injured adolescent. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Adjunctive lisdexamfetamine in bipolar depression: a preliminary randomized, placebo-controlled trial. [2015]

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

The switch mechanism and the bipolar/unipolar dichotomy. [2019]

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

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

5. England pubmed.ncbi.nlm.nih.gov

A review of acute treatments for bipolar depression. [2019]

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

Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. [2015]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of armodafinil in bipolar depression: A 6-month open-label extension study. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of olanzapine monotherapy in acute bipolar depression: a pooled analysis of controlled studies. [2018]

9. Ireland pubmed.ncbi.nlm.nih.gov

Lithium does not attenuate the effects of D-amphetamine in healthy volunteers. [2019]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Dextroamphetamine as a treatment for depression and low energy in AIDS patients: a pilot study. [2019]

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

Placebo effect in randomized, controlled studies of acute bipolar mania and depression. [2019]