What side effects are associated with this type of intervention?

Second-generation antipsychotics, such as aripiprazole, risperidone, and olanzapine, are commonly used to treat schizophrenia. These medications are generally preferred due to their lower risk of extrapyramidal symptoms (e.g., akathisia, dystonia, parkinsonism) compared to first-generation antipsychotics. However, they can still cause side effects such as weight gain, metabolic syndrome, diabetes, and dyslipidemia. GLP-1 receptor agonists like semaglutide, which are being studied for weight management in patients with schizophrenia, have their own side effects, including gastrointestinal issues (e.g., nausea, vomiting), and a potential risk for pancreatitis.

What prior FDA approvals exist?

The FDA has approved several antipsychotic medications for the treatment of schizophrenia, including olanzapine, risperidone, quetiapine, and clozapine. These drugs primarily target dopamine receptors to manage symptoms of psychosis. While GLP-1 receptor agonists like semaglutide are being studied for weight management in patients with schizophrenia, they are not yet approved for treating schizophrenia itself. Traditional antipsychotics remain the mainstay of treatment, with ongoing research into adjunctive therapies to address metabolic side effects.

What other types of research exist?

Promising alternatives to Semaglutide for schizophrenia patients in 2024 include metformin, topiramate, aripiprazole (especially for those on clozapine), and liraglutide. Each of these medications has shown efficacy in weight management and metabolic control in this population.

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GLP-1 Receptor Agonist

Semaglutide for Schizophrenia and Obesity (Sema Trial)

N/A

Recruiting

Led By Margaret Hahn, MD, PhD

Research Sponsored by Centre for Addiction and Mental Health

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Must not have

Type 1 Diabetes (T1D) or current diagnosis of Type 2 Diabetes (T2D), diagnosis of T2D on OGTT screen, or HbA1c > 6.5%

History of pancreatitis or elevated amylase on screen

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 32 weeks

Summary

This trial is testing a medication to help overweight or obese patients with schizophrenia who are on antipsychotics and haven't lost enough weight with metformin. The medication works by making you feel full sooner and helping your body use insulin better. It has been shown to induce significant weight loss in individuals with obesity or overweight.

Who is the study for?

This trial is for adults aged 18-65 with schizophrenia spectrum disorder or related conditions, who are obese due to antipsychotic medications and haven't lost weight on metformin. Participants must have a BMI of at least 30, or 27 with certain health issues, and can't be pregnant, nursing, or without contraception if applicable.

What is being tested?

The study tests whether semaglutide helps overweight individuals with schizophrenia spectrum disorders lose weight compared to a placebo. These patients struggle with obesity partly because of their antipsychotic medication and haven't had success losing weight on metformin.

What are the potential side effects?

Semaglutide may cause side effects like digestive problems (nausea, vomiting), low blood sugar levels especially in those taking other diabetes medicines, pancreatitis risk increase, gallbladder issues such as gallstones.

Eligibility Criteria

Exclusion Criteria

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

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I have diabetes, with an HbA1c level over 6.5%.

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I have had pancreatitis or high amylase levels.

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I am taking medication for weight loss, blood thinning, or that affects my kidneys.

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I have liver or kidney problems.

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I have a history of blood sugar dropping suddenly.

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I or my family have a history of thyroid cancer or multiple endocrine neoplasia.

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I have a history of heart rhythm problems.

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I have a thyroid condition that is not well-managed.

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I have not had a major medical or surgical event in the last 3 months.

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I am a woman of childbearing age not using birth control, nursing, or pregnant.

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I haven't taken GLP-1RA in the last 3 months or couldn't tolerate it.

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I have a serious heart, blood, lung, or hormone-related condition that is not under control.

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I have a severe stomach or intestine disease.

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I have a history of gallstones or am at risk for gallbladder issues, and my gallbladder has not been removed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 32 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~32 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 32 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

Weight change

Secondary study objectives

Body Mass Index (BMI)

Change in cognitive performance

Lipids

+14 more

Other study objectives

1H-Magnetic resonance spectroscopy (MRS)

Arterial spin labeling (ASL)

Resting state functional MRI (rsfMRI)

+1 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

Semaglutide medication will be taken by participants on a weekly schedule, and adherence tracked

Group II: PlaceboPlacebo Group1 Intervention

Placebo will be taken by participants on a weekly schedule, and adherence tracked

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Semaglutide

2021

Completed Phase 4

~5160

0 / 14Eligibility 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 schizophrenia primarily involve antipsychotic medications that target dopaminergic neurotransmission. Typical antipsychotics, such as haloperidol, block dopamine D2 receptors, reducing symptoms like hallucinations and delusions. Atypical antipsychotics, including clozapine and risperidone, also target serotonin receptors, which can help with both positive and negative symptoms of schizophrenia. These mechanisms are crucial as they address the dopamine dysregulation believed to underlie many schizophrenia symptoms. Emerging treatments like GLP-1 receptor agonists, such as Semaglutide, are being studied for their potential to modulate dopamine-mediated pathways and offer additional benefits like weight management, which is particularly relevant for patients on antipsychotic medications.

When the drugs don't work: the potential of glutamatergic antipsychotics in schizophrenia.Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis.Glutamatergic drugs for schizophrenia.