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Study on Esketamine and Diphenhydramine for Treating Depression and Negative Symptoms in Schizophrenia Patients

Verified siteRegistered 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 esketamine on patients with schizophrenia or schizoaffective disorder, specifically targeting negative and depressive symptoms. Esketamine is a medication that will be compared to a placebo to see if it can better reduce these symptoms. The study aims to determine if esketamine is more effective than the placebo in improving the mental health of individuals with these conditions.

Participants in the study will receive treatments over a period of time, with some receiving esketamine and others receiving a placebo. The placebo used in this study is diphenhydramine, which is commonly known for its use in allergy relief. The study will monitor changes in symptoms using specific scales designed to measure negative and depressive symptoms in schizophrenia and schizoaffective disorder.

The trial will involve a series of treatments and assessments to track the progress of participants. The goal is to observe any changes in symptoms from the beginning of the study to the end, providing valuable information on the effectiveness of esketamine as a treatment option for these mental health conditions. The study is expected to continue until November 2025.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial assessment

    An initial assessment is conducted to confirm eligibility for the study. This includes verifying a diagnosis of schizophrenia or schizoaffective disorder, as well as ensuring stable medication use for at least four weeks prior to the study.

    Eligibility is determined based on specific criteria, such as age between 18 and 65 years, and the ability to provide written consent.

  2. Step 2

    Baseline evaluation

    A baseline evaluation is performed to measure current symptoms using the Brief Negative Symptom Scale (BNSS) and the Montgomery-Asberg Depression Rating Scale (MADRS).

    These scores will serve as a reference point for assessing changes during the trial.

  3. Step 3

    Treatment phase 1

    The first treatment phase involves receiving either esketamine hydrochloride or an active placebo, diphenhydramine hydrochloride, through an intravenous infusion.

    The treatment is administered as a solution for injection, with the specific dosage and frequency determined by the study protocol.

  4. Step 4

    Midpoint evaluation

    After two weeks of treatment, a midpoint evaluation is conducted to assess changes in symptoms using the BNSS and MADRS scales.

    This evaluation helps determine the effectiveness of the treatment received during the first phase.

  5. Step 5

    Treatment phase 2

    Participants switch to the alternative treatment for another two-week period. Those who received esketamine in the first phase will now receive the active placebo, and vice versa.

    The administration method remains the same, with intravenous infusions of the solution for injection.

  6. Step 6

    Final evaluation

    A final evaluation is conducted at the end of the second treatment phase to measure any changes in symptoms using the BNSS and MADRS scales.

    This evaluation provides data on the overall effectiveness of the treatments in reducing negative and depressive symptoms.

Who can join the trial?

7 criteria

  • Have a diagnosis of schizophrenia according to the DSM-5, which is a guide used by doctors to identify mental health conditions.
  • Have a minimum score of 39 on the Brief Negative Symptom Scale (BNSS), which measures the severity of certain symptoms, or
  • Have a minimum score of 22 on the Montgomery-Åsberg Depression Rating Scale (MADRS), which measures the level of depression.
  • Be between 18 and 65 years old.
  • Be able to provide written informed consent, meaning you understand the study and agree to participate.
  • Have been on stable medication for mental health for at least four weeks before joining the study.
  • If you are a female who can have children, you need to use a reliable method of birth control, such as the pill, vaginal ring, hormonal patch, intrauterine device, cervical cap, condom, contraceptive injection, or diaphragm.

Who cannot join the trial?

5 criteria

  • Patients who do not have a diagnosis of **schizophrenia** or **schizoaffective disorder**. These are mental health conditions that affect how a person thinks, feels, and behaves.
  • Patients who do not experience **negative symptoms**. These are symptoms that involve a decrease in the ability to function normally, such as lack of emotion or interest in activities.
  • Patients who do not experience **depressive symptoms**. These are symptoms that include feelings of sadness, hopelessness, or a lack of energy.
  • Patients who are not within the specified age range for the study.
  • Patients who are part of a **vulnerable population**. This means groups of people who might be at a higher risk of harm or exploitation.
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Investigated drugs

Esketamine is being studied for its potential to reduce negative and depressive symptoms in patients with schizophrenia. It is a medication that works on the brain's chemical systems and is being tested to see if it can help improve mood and reduce symptoms associated with psychotic disorders.

What is already known about the treatment

Esketamine – Esketamine is administered as a nasal spray, allowing for direct absorption through the nasal mucosa. It is currently being studied in clinical trials for its effectiveness in treating negative and depressive symptoms in patients with schizophrenia or schizoaffective disorder. The main therapeutic indication is to alleviate these symptoms, which are often resistant to traditional treatments. At the molecular level, esketamine works by modulating the activity of the NMDA receptor, a type of glutamate receptor in the brain, which is thought to play a role in mood regulation. It is classified pharmacologically as an NMDA receptor antagonist.

Investigated diseases

  • Schizophrenia

    Schizophrenia is a chronic mental health disorder that affects how a person thinks, feels, and behaves. People with schizophrenia may experience hallucinations, delusions, and disorganized thinking. Negative symptoms include reduced emotional expression and lack of motivation. The disorder can lead to difficulties in social interactions and daily functioning. Symptoms often start in young adulthood and can vary in intensity over time. Schizophrenia requires ongoing management to help individuals lead fulfilling lives.

  • Schizoaffective Disorder

    Schizoaffective disorder is a mental health condition characterized by a combination of schizophrenia symptoms, such as hallucinations or delusions, and mood disorder symptoms, like depression or mania. The disorder can lead to impaired social and occupational functioning. Individuals may experience episodes of mood disturbances along with psychotic symptoms. The course of the disorder can vary, with periods of severe symptoms followed by times of improvement. It is important for individuals to receive appropriate support and management to maintain stability.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-519097-39-01Estimated enrolment20 patientsSponsorMedical University Of Vienna

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