What side effects are associated with this type of intervention?

Common treatments for depression include antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and anti-inflammatory agents like celecoxib. SSRIs can cause side effects such as nausea, insomnia, sexual dysfunction, and weight gain. SNRIs may lead to increased blood pressure, dizziness, and dry mouth. Anti-inflammatory agents like celecoxib can cause gastrointestinal issues, cardiovascular risks, and kidney problems. It is important to discuss these potential side effects with a healthcare provider to determine the most appropriate treatment.

What prior FDA approvals exist?

The FDA has approved several classes of drugs for the treatment of depression, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, and serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine. Augmentation strategies with antipsychotics, such as aripiprazole, have also been approved for treatment-resistant depression. While the role of inflammation in depression is being studied, anti-inflammatory agents are not yet standard treatments for depression. Current research is exploring how reducing inflammation might improve reward processing and alleviate depressive symptoms.

What other types of research exist?

Promising novel alternatives to anti-inflammatory agents for treating depression in 2024 include: 1) Ketamine and esketamine, which have shown rapid antidepressant effects; 2) Psychedelic-assisted therapy, particularly with psilocybin, which is being studied for its potential to alleviate depression; 3) Digital therapeutics and mobile health applications that offer cognitive-behavioral therapy (CBT) and other psychological interventions; 4) Lifestyle interventions such as structured physical exercise programs, which have been shown to reduce depressive symptoms; and 5) Nutritional approaches, including omega-3 fatty acids and other dietary modifications aimed at improving mental health.

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Endotoxin for Depression

Q: What is the mechanism of action of this treatment?

Common treatments for depression often target neurotransmitter systems, such as serotonin, norepinephrine, and dopamine, to improve mood and cognitive function. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) increase the availability of these neurotransmitters in the brain. Additionally, emerging research suggests that inflammation may play a role in depression by affecting reward processing. Anti-inflammatory agents are being studied for their potential to reduce inflammation and improve depressive symptoms. Understanding these mechanisms is crucial for patients, as it can guide personalized treatment plans and improve outcomes by targeting the underlying biological factors contributing to their depression.

Phase 1

Waitlist Available

Led By Chloe C Boyle, PhD

Research Sponsored by University of California, Los Angeles

Eligibility Criteria Checklist

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

Must have

Participants will be 25-44 years of age

Participants will be biologically female and premenopausal (as evaluated by self report)

Must not have

Current and regular use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, aspirin, immune modifying drugs, opioid analgesics, statins, antihypertensive drugs, anti-arrhythmic drugs, and antidepressant medications (none in the last 6 months)

Current history of sleep apnea or nocturnal myoclonus; Phase-shift disorder, which will be identified by the Structured Clinical Interview and the Duke Structured Interview for Sleep Disorders

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 14 days (7 days pre-injection; 7 days post-injection).

Summary

This trial involves creating temporary inflammation in women to observe how it affects their reactions to different rewards, such as money or smiling faces. The goal is to understand how inflammation might contribute to depression and if age makes a difference.

Who is the study for?

This trial is for premenopausal women aged 25-44 in good health, without chronic mental or physical illnesses, not taking certain medications like steroids or antidepressants, and who haven't worked night shifts or traveled across time zones recently. They should have no history of severe allergies, autoimmune diseases, fainting during blood draws, obesity (BMI > 35), drug use, or significant lab test abnormalities.

What is being tested?

The study investigates how inflammation affects the reward system in younger women and its link to depression. It involves comparing the effects of an endotoxin (which can cause temporary inflammation) with a placebo on participants' responses to different rewards such as money or positive images.

What are the potential side effects?

Potential side effects from the endotoxin may include flu-like symptoms such as fever, chills, headache, muscle pain and weakness due to induced inflammation. The placebo is unlikely to cause any direct side effects but could result in a reaction if there's an expectation of feeling unwell.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am between 25 and 44 years old.

Select...

I am a premenopausal woman.

Select...

I am between 25 and 44 years old.

Select...

I am a premenopausal woman.

Exclusion Criteria

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

Select...

I haven't taken any prescription drugs like steroids or painkillers in the last 6 months.

Select...

I have been diagnosed with sleep apnea, nocturnal myoclonus, or a phase-shift disorder.

Select...

I have a history of severe allergies, autoimmune, liver, or other chronic diseases.

Select...

I have an autoimmune disorder like rheumatoid arthritis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 14 days (7 days pre-injection; 7 days post-injection).

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~14 days (7 days pre-injection; 7 days post-injection).

This trial's timeline: 3 weeks for screening, Varies for treatment, and 14 days (7 days pre-injection; 7 days post-injection). for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

General social reward response (reward sensitivity and motivation)

Non-social (monetary) reward response (reward motivation, learning, sensitivity)

Secondary study objectives

Anticipatory and Consummatory Daily Reward Response

Close social reward response

Mental Depression

+1 more

Other study objectives

Positive and negative emotion regulation capacity

Side effects data

From 2016 Phase 1 & 2 trial • 10 Patients • NCT00923910

100%

Platelets-low

80%

Glucose, serum-low (hypoglycemia)

80%

Hemoglobin-low

80%

Pruritis/itching

80%

Leukocytes (total WBC) - low

80%

Rash/desquamation

80%

Neutrophils/granulocytes (ANC/AGC) - low

60%

Sodium, serum-low (hyponatremia)

60%

ALT, SGPT (serum glutamic pyruvic transaminase) - high

60%

AST, SGOT (serum glutamic oxaloacetic transaminase) - high

60%

Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0x10e9/L)

60%

Pain: Abdomen NOS

40%

Supraventricular and nodal arrhythmia: sinus tachycardia

40%

Mood alteration:anxiety

40%

Albumin, serum low (hypoalbuminemia)

40%

Glucose (serum -high (hyperglycemia)

40%

Bicarbonate, serum low

40%

Diarrhea

40%

PTT (partial thromboplastin time)

40%

Magnesium, serum high (hypermagnesemia)

40%

Magnesium, serum low (hypomagnesemia)

40%

Pain: Head/Headache

40%

Potassium, serum-low (hypokalemia)

40%

Cough

40%

Nausea

40%

Pain: throat/pharynx/larynx

40%

Calcium, serum-low (hypocalcemia)

20%

Phosphate, serum low (hypophosphatemia)

20%

Supraventricular and nodal arrhythmia: sinus bradycardia

20%

Potassium, serum-high (hyperkalemia)

20%

Proteinuria

20%

Triglyceride, serum high (hypertriglyceridemia)

20%

Sodium, serum-high (hypernatremia)

20%

Infection with normal ANC or Grade 1 or 2 neutrophils:lung (pneumonia)

20%

Pain: chest wall

20%

Dry eye syndrome

20%

Infection with normal ANC or Grade 1 or 2 neutriphils:lung (pneumonia)

20%

GGT (gamma-Glutamyl transpeptidase)

20%

Allergy/Immunology - Other, Specify - allergy to Sorbaview

20%

Bruising (in absence of Grade 3 or 4 thrombocytopenia)

20%

Insomnia

20%

Rigors/chills

20%

Pain: neck

20%

Cholesterol, serum-high (hypercholesteremia)

20%

Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)

20%

Hypotension

20%

Fatigue (asthenia, lethargy, malaise)

20%

Coagulation - Other, Specify - PT, prolonged

20%

Hemorrhage, pulmonary/upper respiratory: Nose

20%

Hepatobiliary/pancreas- Other, Specify - non-alcoholic Steatoheptits

20%

Esophagitis

20%

Febrile neutropenia

20%

Anorexia

20%

Iron overload

20%

Infection with unknown ANC:sinus

20%

Pain:muscle

20%

Pain:pain NOS

20%

Ocular/Visual - Other, Specify - Eye drainage

20%

Pain: Eye

20%

Striae

20%

Uric acid, serum high (hyperuricemia)

20%

Urinary frequency/urgency

20%

Vision-blurred vision

20%

Infection with normal ANC or Grade 1 or 2 neutrophils: upper airway NOS

20%

Pain:Joint

20%

Sweating (diaphoresis)

20%

Bilirubin (hyperbilirubinemia)

100%

80%

60%

40%

20%

Study treatment Arm

Recipients

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: EndotoxinExperimental Treatment1 Intervention

Endotoxin 0.8 ng/kg body weight; 1 infusion

Group II: PlaceboPlacebo Group1 Intervention

same volume of 0.9% saline

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Endotoxin

2008

Completed Phase 4

~660

0 / 8Eligibility 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 often target neurotransmitter systems, such as serotonin, norepinephrine, and dopamine, to improve mood and cognitive function. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) increase the availability of these neurotransmitters in the brain. Additionally, emerging research suggests that inflammation may play a role in depression by affecting reward processing. Anti-inflammatory agents are being studied for their potential to reduce inflammation and improve depressive symptoms. Understanding these mechanisms is crucial for patients, as it can guide personalized treatment plans and improve outcomes by targeting the underlying biological factors contributing to their depression.

Changes in RNA expression levels during antidepressant treatment: a systematic review.