Escitalopram for Brain Tumor

Overseen By IIT Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Nebraska

Must be taking: SSRIs

Must not be taking: Antidepressants

Disqualifiers: Severe renal impairment, Depression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 29

Duration: 12 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants are not already taking an anti-depressant (SSRI or NSRI), so you may need to stop these medications before joining.

What data supports the effectiveness of the drug Escitalopram for brain tumors?

Some research suggests that psychiatric drugs like escitalopram may have potential anticancer properties, showing promise in brain tumor treatment strategies. However, more studies are needed to confirm these effects and understand how they might work in treating brain cancer. ^{1 2 3 4 5}

Is escitalopram safe for use in humans?

Escitalopram, also known as Lexapro, has been studied for its safety in treating depression and anxiety. It is generally well-tolerated with mild side effects, as shown in studies involving children and adolescents with cancer. ^{4 6 7 8 9}

How is the drug escitalopram unique in treating brain tumors?

Escitalopram, typically used as an antidepressant, is unique in treating brain tumors because it can cross the blood-brain barrier and potentially inhibit tumor growth by affecting neurotransmitter levels and neuronal activity in the tumor environment. This repurposing of a psychiatric drug for cancer treatment offers a novel approach compared to traditional cancer therapies. ^{2 3 4 10 11}

What is the purpose of this trial?

This pilot study will include grade IV glioma patients treated with SSRIs during approximately a 17 week study period. Changes in cognition and evaluation of psychosocial factors from baseline to after 17 weeks of treatment with SSRI study drug will be calculated.

Research Team

Nicole A Shonka, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This study is for adults over 19 with a specific brain tumor called Grade IV glioma, who are about to start or are currently receiving chemo and/or radiation. They should be able to perform daily activities (ECOG 0-2), have a life expectancy over 6 months, and not be pregnant. Those with severe kidney issues, depression or anxiety, visual field defects, or intolerance to similar medications cannot join.

Inclusion Criteria

Written informed consent to participate in the study

Life expectancy greater than 6 months

I am about to start chemotherapy or radiation for my newly diagnosed condition.

Exclusion Criteria

I am currently on an SSRI or SNRI antidepressant.

I am a woman who is postmenopausal, had no periods for 2+ years, am sterilized, or will use two forms of birth control.

I had side effects from SSRI or SNRI medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escitalopram 10 mg daily for 90 days to address cognitive dysfunction

12 weeks

Baseline, 12 weeks, and 17 weeks assessments

Follow-up

Participants are monitored for changes in cognition and psychosocial functions after treatment

5 weeks

17 weeks assessment

Treatment Details

Interventions

• Escitalopram

Trial Overview The trial tests Escitalopram Oral Capsules on patients with grade IV glioma over approximately 17 weeks. It aims to see how the drug affects cognition and psychosocial factors in these patients during their treatment period.

Participant Groups

Group I: Escitalopram Experimental Treatment 1 Intervention

This is an open-label study. Escitalopram will be administered to all participants as 10 mg capsules to be taken by mouth daily for 90 days.

Escitalopram is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lexapro for:

• Major depressive disorder
• Generalized anxiety disorder

Approved in European Union as Cipralex for:

• Major depressive episodes
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder with or without agoraphobia
• Obsessive-compulsive disorder

Approved in Canada as Cipralex for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Nicole Shonka

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

In a study of 497 glioblastoma patients, the use of selective serotonin reuptake inhibitors (SSRIs) did not show a significant association with improved overall survival, indicating that SSRIs may not enhance survival outcomes in these patients.

Despite the lack of survival benefit from SSRIs alone, further research is needed to explore their potential effects when combined with other treatments, such as immunotherapies, for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective survival analysis of Glioblastoma patients treated with selective serotonin reuptake inhibitors. Otto-Meyer, S., DeFaccio, R., Dussold, C., et al.[2021]

In a pooled analysis of over 1700 glioblastoma patients, antidepressant use at baseline or the start of maintenance therapy did not significantly affect progression-free survival (PFS) or overall survival (OS), suggesting limited efficacy in improving survival outcomes.

However, patients using antidepressants at the start of maintenance cycle 4 experienced significantly worse overall survival, indicating a potential negative impact that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of antidepressant drug use with outcome of patients with glioblastoma. Seliger, C., Oppong, FB., Lefranc, F., et al.[2023]

Recent research has shown that certain psychiatric drugs, including valproic acid, fluoxetine, escitalopram, and aripiprazole, may have potential in treating malignant brain tumors, highlighting their anticancer properties through various laboratory and clinical studies.

The review emphasizes the need to address limitations in repurposing these medications for brain cancer treatment, particularly for vulnerable populations like children and pregnant women, while suggesting future research directions to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer. Zhuo, C., Xun, Z., Hou, W., et al.[2020]

Imipramine and citalopram, both used for treating depression, may offer potential benefits for patients with malignant glioma, suggesting a need for large epidemiological studies to explore their efficacy in this context.

Recent studies have shown that digoxin, a heart failure medication, can provide unexpected benefits in prostate cancer treatment, highlighting the importance of investigating the effects of existing drugs in new patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voltage-dependent K+ channels as oncotargets in malignant gliomas. Lefranc, F., Pouleau, HB., Rynkowski, M., et al.[2021]

In a 12-week study involving 79 breast cancer outpatients, escitalopram significantly reduced depression symptoms and improved quality of life, with noticeable improvements starting as early as one week into treatment.

By the end of the study, 45.1% of participants showed a significant response to treatment (at least a 50% decrease in depression scores), and 30.6% achieved remission, indicating escitalopram's efficacy in managing depression in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid improvement of depression and quality of life with escitalopram treatment in outpatients with breast cancer: a 12-week, open-label prospective trial. Park, HY., Lee, BJ., Kim, JH., et al.[2013]

Citalopram was well tolerated in a small open-label study of four pediatric oncology patients with depression, suggesting it may be a safe option for this vulnerable population.

Preliminary data indicate that citalopram could be effective as an antidepressant in pediatric oncology patients, offering potential advantages over fluoxetine, particularly in terms of drug interactions and half-life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram to treat depression in pediatric oncology. DeJong, M., Fombonne, E.[2022]

In a 24-week study involving 357 patients with moderate to severe major depressive disorder, escitalopram was found to be at least as effective as citalopram, with statistically significant superiority in improving overall severity of depression by Week 24.

Both medications were safe and well tolerated, but escitalopram had fewer patient withdrawals compared to citalopram, highlighting its potential for better long-term adherence in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder. Colonna, L., Andersen, HF., Reines, EH.[2022]

In a study of 32 pediatric cancer patients aged 2-21, both SSRIs and mirtazapine were found to be effective in improving psychiatric symptoms, with 84% of patients showing improvement after treatment.

The antidepressants were well tolerated, with only mild adverse events reported, suggesting they are safe options for managing depression and anxiety in children and adolescents with cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antidepressant Treatment. Lavan, O., Peled, O., Avishai-Neumann, M., et al.[2022]

In a study of 283 patients with brain tumors, 15.4% of those treated with antiepileptic drugs (AEDs) experienced treatment emergent psychiatric adverse events (TE-PAEs), particularly associated with tumors in the frontal lobe and the use of levetiracetam.

The findings suggest that using an alternative AED to levetiracetam may help reduce the risk of developing psychiatric symptoms in patients with frontal lobe tumors, highlighting the importance of considering drug choice in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain tumor location influences the onset of acute psychiatric adverse events of levetiracetam therapy: an observational study. Belcastro, V., Pisani, LR., Bellocchi, S., et al.[2018]

Psychotropic drugs, such as antipsychotics and antidepressants, can cross the blood-brain barrier and may inhibit the growth of glioma by affecting key signaling pathways involved in cell proliferation and apoptosis.

These drugs have shown potential as anticancer agents in preclinical and clinical studies, suggesting they can be repurposed for glioma treatment while maintaining their established safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug repositioning: Using psychotropic drugs for the treatment of glioma. You, F., Zhang, C., Liu, X., et al.[2022]

Valproate (VPA) shows promise in treating glioblastoma multiforme by inhibiting tumor growth through mechanisms such as histone deacetylase inhibition, which leads to gene transcription changes that promote cell differentiation and reduce invasion.

VPA may enhance the effectiveness of traditional treatments like chemotherapy and radiation by inhibiting DNA repair, suggesting that combining VPA with these therapies could be a beneficial strategy for glioblastoma patients, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valproic acid for the treatment of malignant gliomas: review of the preclinical rationale and published clinical results. Berendsen, S., Broekman, M., Seute, T., et al.[2013]

References

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

A retrospective survival analysis of Glioblastoma patients treated with selective serotonin reuptake inhibitors. [2021]

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

Association of antidepressant drug use with outcome of patients with glioblastoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer. [2020]

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

Voltage-dependent K+ channels as oncotargets in malignant gliomas. [2021]

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

Rapid improvement of depression and quality of life with escitalopram treatment in outpatients with breast cancer: a 12-week, open-label prospective trial. [2013]

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

Citalopram to treat depression in pediatric oncology. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder. [2022]

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

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antidepressant Treatment. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Brain tumor location influences the onset of acute psychiatric adverse events of levetiracetam therapy: an observational study. [2018]

10. Ireland pubmed.ncbi.nlm.nih.gov

Drug repositioning: Using psychotropic drugs for the treatment of glioma. [2022]

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

Valproic acid for the treatment of malignant gliomas: review of the preclinical rationale and published clinical results. [2013]