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Esketamine Nasal Spray for Patients with Treatment-Resistant Bipolar Depression

Fast replyRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying the effects of a medication called Spravato, which is a nasal spray containing the active substance esketamine. The study is specifically looking at its use in treating bipolar disorder during depressive episodes, particularly in cases where the depression has not responded to other treatments. This condition is often referred to as treatment-resistant bipolar depression.

The purpose of the study is to evaluate how effective and safe Spravato is for patients with this type of depression. Participants in the study will use the nasal spray, and researchers will monitor their response to the treatment over a period of time. The study is designed to gather information on how well the medication works and to observe any side effects that may occur. This information will help determine if Spravato could be a viable treatment option for those who have not found relief with other medications.

Throughout the study, participants will be closely observed to ensure their safety and to track any changes in their symptoms. The study will also look at how well participants tolerate the medication, which means checking if they can continue using it without significant issues. The findings from this trial may lead to further research, including more extensive studies that compare Spravato to a placebo, to better understand its potential benefits and risks for people with treatment-resistant bipolar depression.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial assessment

    Upon joining the study, an initial assessment is conducted to confirm eligibility. This includes verifying a diagnosis of bipolar I or II disorder, ensuring age is between 18 and 75, and confirming a current depressive episode with a MADRS score above 18.

    Eligibility also requires a history of treatment-resistant depression, defined as a lack of response to at least two different antidepressant or mood-stabilizing medications. Current treatment with a mood stabilizer at a stable dosage for at least two weeks is necessary.

  2. Step 2

    Medication administration

    The medication used in this trial is Spravato (esketamine) nasal spray, administered intranasally. The dosage is 28 mg per administration.

    The medication is administered twice a week, specifically on Mondays and Fridays, under supervision to ensure correct usage and monitor immediate effects.

  3. Step 3

    Monitoring and evaluation

    Throughout the trial, regular monitoring is conducted to assess the efficacy and safety of the treatment. Efficacy is measured by the reduction in MADRS scores, with a 50% reduction indicating a response and a score below ten indicating remission.

    Safety is evaluated by tracking side effects, including psychiatric symptoms like mania, psychosis, and suicidality, as well as physical side effects. Tolerability is assessed by monitoring dropout rates.

  4. Step 4

    Follow-up assessments

    Follow-up assessments are conducted to monitor for any relapse, defined by increased depressive symptoms, hospital admissions, or suicide attempts.

    These assessments help determine the long-term effects of the treatment and any potential need for additional interventions.

Who can join the trial?

8 criteria

  • Have a diagnosis of bipolar I or II disorder. This means you have been identified as having one of these types of bipolar disorder by a healthcare professional.
  • Be between the ages of 18 and 75.
  • Have MADRS scores above 18. MADRS stands for Montgomery-Åsberg Depression Rating Scale, which is a tool used to measure the severity of depression.
  • Currently experiencing a depressive episode. This means you are in a period where you feel very low or depressed.
  • Meet the criteria for treatment-resistant depression. This means you have not responded to at least two different medications for depression or mood stabilization, even after taking them for a sufficient time and at the right dosage.
  • Currently taking a mood stabilizer, but have not been treated with more than five different antidepressant therapies for the current depressive episode.
  • Your medication dosage has been stable for at least two weeks. This means you have been taking the same amount of medication without changes for at least two weeks.
  • Be available on Monday and Friday for study visits or procedures.

Who cannot join the trial?

5 criteria

  • Patients who do not have a diagnosis of bipolar disorder with a depressive episode cannot participate. Bipolar disorder is a mental health condition that causes extreme mood swings, including emotional highs (mania or hypomania) and lows (depression).
  • Patients who are not within the specified age range cannot participate. The age range for this study is from 18 to 65 years old.
  • Patients who are not able to use the esketamine nasal spray as directed cannot participate. Esketamine is a medication used to treat depression, and it is administered through the nose.
  • Patients who have not shown resistance to other treatments for bipolar depression cannot participate. Treatment-resistant means that previous treatments have not been effective.
  • Patients who are part of a vulnerable population, such as those who cannot give informed consent, cannot participate. Informed consent means understanding the study and agreeing to take part.
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Investigated drugs

Esketamine Nasal Spray (Spravato) is being studied for its potential to help people with bipolar depression who have not responded to other treatments. This medication is used as a nasal spray, which means it is administered through the nose. The goal of the trial is to see how effective the nasal spray is in improving symptoms of depression and to ensure it is safe and well-tolerated by patients.

What is already known about the treatment

Esketamine – Esketamine is administered as a nasal spray and is currently being studied for its effectiveness in treating therapy-resistant bipolar depression. It is in the pilot trial phase, focusing on safety and tolerability, with the potential to lead to more extensive trials. The main therapeutic indication is for depressive episodes in bipolar disorder. Esketamine works by modulating the activity of glutamate, a neurotransmitter in the brain, which can help alleviate symptoms of depression. It is classified pharmacologically as an NMDA receptor antagonist.

Investigated diseases

Bipolar Disorder - Depressive Episode – This condition is a phase of bipolar disorder characterized by prolonged periods of depression. Individuals may experience persistent sadness, loss of interest in activities, and feelings of hopelessness. Energy levels are often low, and there may be changes in sleep patterns and appetite. Cognitive functions such as concentration and decision-making can be impaired. This depressive episode can last for weeks or even longer, significantly impacting daily life and functioning. It is one part of the broader bipolar disorder, which also includes episodes of mania or hypomania.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2023-508125-27-00Estimated enrolment20 patientsSponsorLeids Universitair Medisch Centrum (LUMC)

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