What side effects are associated with this type of intervention?

Common treatments for depression include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and atypical antidepressants. Known side effects of these treatments can include nausea, weight gain, sexual dysfunction, insomnia, dry mouth, blurred vision, and constipation. For GLP-1 receptor agonists like Semaglutide, which are being studied for their potential neuroprotective and anti-inflammatory effects, common side effects include gastrointestinal issues such as nausea and vomiting. Further research is needed to fully understand the side effects of GLP-1 receptor agonists when used specifically for treating depression.

What prior FDA approvals exist?

The FDA has approved various drugs for the treatment of depression, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants. While Semaglutide, a GLP-1 receptor agonist, is primarily used for type 2 diabetes and obesity, it is being studied for its potential neuroprotective and anti-inflammatory effects in treating cognitive dysfunction in major depressive disorder (MDD). Similar GLP-1 receptor agonists like liraglutide have shown benefits in other conditions but are not yet approved specifically for depression.

What other types of research exist?

Promising novel alternatives to Semaglutide for depression treatment in 2024 include: 1) Ketamine and its derivatives (e.g., Esketamine) which have rapid-acting antidepressant effects and potential neuroprotective properties. 2) Psilocybin, a psychedelic compound showing efficacy in treatment-resistant depression and potential anti-inflammatory effects. 3) Brexanolone, a neurosteroid approved for postpartum depression, with ongoing research for broader depressive disorders. 4) Anti-inflammatory agents like minocycline, which are being investigated for their potential to reduce neuroinflammation associated with depression.

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Glucagon-like peptide-1 receptor agonist

Semaglutide for Cognitive Impairment in Depression

Phase 2

Waitlist Available

Led By Rodrigo B. Mansur, MD, PhD

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Overweight (i.e. BMI ≥ 25 kg/m2)

Individuals between the ages of 18 and 60 who meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for MDD

Must not have

History of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration

Diagnosis of possible or probable Alzheimer's Disease, Mild Cognitive Impairment, or any other dementia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 16 weeks

Summary

This trial will test if semaglutide can improve thinking skills in overweight people with depression. Semaglutide is a medication that helps control blood sugar and might also help the brain work better. It is used for weight loss and blood sugar control, and has shown potential benefits for brain function.

Who is the study for?

This trial is for adults aged 18-60 with major depressive disorder (MDD) who have cognitive issues and are overweight. Participants must perform below average on a specific cognitive test and not be severely depressed, drug-dependent, pregnant, or breastfeeding. They can't have certain mental health conditions or be taking diabetes medications.

What is being tested?

The study tests if semaglutide improves brain function in people with MDD. It's a comparison between semaglutide and a placebo (a substance with no active drug). Participants will receive either the real medication or placebo without knowing which one they're getting.

What are the potential side effects?

Semaglutide may cause digestive problems like nausea, vomiting, diarrhea; risk of low blood sugar; possible thyroid tumors; pancreatitis; allergic reactions; kidney problems; changes in vision due to diabetic retinopathy.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My BMI is 25 or higher, indicating I am overweight.

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I am between 18 and 60 years old and have been diagnosed with major depression.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of neurological disorders or illnesses that could affect my thinking.

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I have been diagnosed with Alzheimer's, Mild Cognitive Impairment, or another form of dementia.

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I am experiencing a severe episode of depression.

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I cannot take semaglutide due to allergies, liver or severe kidney problems, or a family history of certain cancers.

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I have been diagnosed with OCD, PTSD in the last year, or borderline personality disorder.

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I have had pancreatitis or pancreatic cancer.

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I have had diabetic eye disease in the past.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 16 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~16 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 16 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Executive Function Composite Score

Secondary study objectives

36-Item Short Form Health Survey (SF-36)

Diet History Questionnaire III (DHQ)

Digit Symbol Substitution Test (DSST)

+11 more

Side effects data

From 2020 Phase 4 trial • 104 Patients • NCT04189848

21%

Nausea

12%

Decreased Appetite

100%

80%

60%

40%

20%

Study treatment Arm

Overall Study

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: SemaglutideExperimental Treatment1 Intervention

Participants receive semaglutide once daily orally, initiated at 3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks (i.e., duration of 16 weeks in total).

Group II: PlaceboPlacebo Group1 Intervention

Participants receive matching semaglutide placebo capsules once daily (duration of 16 weeks).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Semaglutide

2021

Completed Phase 4

~5160

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for depression include selective serotonin reuptake inhibitors (SSRIs), which increase serotonin levels in the brain, and serotonin-norepinephrine reuptake inhibitors (SNRIs), which boost both serotonin and norepinephrine. These treatments aim to correct chemical imbalances that affect mood and emotional state. Emerging treatments like GLP-1 receptor agonists, such as Semaglutide, show potential due to their neuroprotective and anti-inflammatory effects. These mechanisms may help reduce neuronal apoptosis and inflammation, which are linked to depression. Understanding these mechanisms is crucial for patients as it opens new avenues for treatment, especially for those who do not respond well to traditional antidepressants.

Metformin is Protective Against the Development of Mood Disorders.A distinct transcriptional signature of antidepressant response in hippocampal dentate gyrus granule cells.Possible role of GLP-1 in antidepressant effects of metformin and exercise in CUMS mice.