Sertraline for Depression

(Re-EMBARC Trial)

Overseen By Lauren Enten, B.S.A

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas at Austin

Must be taking: SSRIs

Must not be taking: Antipsychotics, Mood stabilizers

Disqualifiers: Psychosis, Bipolar, Substance-use, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to use brain scans to predict how well patients with major depression will respond to the antidepressant sertraline. Sertraline, one of the oldest antidepressants, remains the most effective treatment for depression. By identifying specific brain activity patterns, doctors hope to better tailor treatments for each patient, improving outcomes for those who may not respond to typical treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that might interfere with the study drug, such as antipsychotics and mood stabilizers. If you're on these medications, you may need to stop them to participate.

What data supports the effectiveness of the drug Sertraline for treating depression?

Research shows that Sertraline is effective in treating major depressive disorder and dysthymic disorder in adolescents, with significant improvements observed in depression and anxiety symptoms over a six-month period. Additionally, multicenter studies have demonstrated its efficacy in treating depression and obsessive-compulsive disorder in adults. ^{1 2 3 4 5}

Is sertraline generally safe for humans?

Sertraline, also known as Zoloft, is generally considered safe for treating depression and other disorders, but it can cause side effects like nausea, diarrhea, insomnia, and dizziness. Rarely, it may cause serious heart issues, as seen in a case of sinus arrest (a type of heart rhythm problem). ^{2 4 6 7 8}

How does the drug Sertraline differ from other treatments for depression?

Sertraline is unique because it is a selective serotonin reuptake inhibitor (SSRI), which means it works by increasing the levels of serotonin (a chemical that affects mood) in the brain, unlike other types of antidepressants that may target different neurotransmitters or have different mechanisms of action. ^{9 10 11 12 13}

Eligibility Criteria

This trial is for English-speaking adults with early-onset major depression, diagnosed per DSM-5 criteria. Participants must have had multiple depressive episodes or one lasting over two years and a significant level of current depression symptoms. They should be able to undergo MRI and EEG scans but not be at high suicide risk or have conditions like psychosis, bipolar disorder, substance abuse, unstable medical issues, contraindications to MRI, or certain treatments for depression.

Inclusion Criteria

English as primary language, and comprehension suitable to understand experimenter instructions

Meet criteria for a current major depressive episode diagnosed through the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) (SCID-5)

My depression score is above 14 before starting Sertraline.

Exclusion Criteria

I have not had an antidepressant fail to work for me in this current episode, according to the MGH standards.

I have a history of serious brain conditions or injuries.

I am currently receiving therapy for depression.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo fMRI and EEG assessments to establish baseline brain function prior to treatment initiation

1 week

1 visit (in-person)

Treatment

Participants receive sertraline treatment, with clinical assessments of outcomes over 8 weeks

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Sertraline

Trial Overview The study aims to find brain biomarkers that predict how well individuals with major depression will respond to Sertraline (Zoloft), an SSRI antidepressant. Researchers will use fMRI and EEG to measure brain activity and connections before treatment begins.

Participant Groups

Group I: Sertraline hydrochloride, up to 200mg/day or maximum tolerable dose Experimental Treatment 1 Intervention

Established FDA-approved treatment for major depressive disorder

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

Approved in United States as Zoloft for:

• Depression
• Obsessive-compulsive disorder (OCD)
• Panic disorder
• Post-traumatic stress disorder (PTSD)
• Premenstrual dysphoric disorder (PMDD)
• Social anxiety disorder

Approved in European Union as Sertraline for:

• Major depressive episodes
• Panic disorder
• Obsessive compulsive disorder
• Social anxiety disorder
• Post traumatic stress disorder
• Premenstrual dysphoric disorder

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Lehigh University

Collaborator

Trials

24

Recruited

6,800+

Findings from Research

In a 6-month study of 21 adolescents with major depressive disorder (MDD) and dysthymic disorder (DD), sertraline demonstrated significant efficacy, with 100% of MDD completers responding to treatment by week 24.

Sertraline was generally safe and well tolerated, with most side effects being mild to moderate, indicating it could be a suitable option for treating depression in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline effects in adolescent major depression and dysthymia: a six-month open trial. Nixon, MK., Milin, R., Simeon, JG., et al.[2013]

Coadministration of sertraline with cisapride significantly reduced cisapride plasma concentrations (by 29% for Cmax and 36% for AUC), but did not affect QTc intervals, indicating a safe interaction.

In contrast, sertraline increased pimozide plasma concentrations (by 35% for Cmax and 37% for AUC) without prolonging QTc intervals, suggesting that the interaction mechanisms may involve factors beyond the CYP3A4 enzyme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coadministration of sertraline with cisapride or pimozide: an open-label, nonrandomized examination of pharmacokinetics and corrected QT intervals in healthy adult volunteers. Alderman, J.[2022]

Sertraline is effective for treating mood and anxiety disorders in both adults and children, but it is not FDA-approved for pediatric use, despite its increasing popularity due to a better side effect profile compared to older antidepressants.

Sertraline is considered safer in overdose situations than tricyclic antidepressants, although cases of overdose in children are rare, highlighting the need for careful monitoring and management in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric sertraline overdose. Catalano, G., Cooper, DS., Catalano, MC., et al.[2022]

Sertraline hydrochloride effectively blocks the reuptake of serotonin in the brain, making it a promising treatment for depression and obsessive-compulsive disorder, with a recommended daily dose of 50 to 200 mg.

The medication has a favorable safety profile compared to tricyclic antidepressants, although it can cause gastrointestinal side effects like nausea and diarrhea, similar to those seen with fluoxetine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline: a new specific serotonin reuptake blocker. Guthrie, SK.[2019]

In a 6-week study involving 286 psychiatric outpatients, sertraline was found to be significantly more effective than fluoxetine for treating major depression in patients with psychomotor agitation, with a response rate of 62% compared to 39%.

Secondary efficacy measures also showed greater improvement in the sertraline group across various depression and anxiety scales, suggesting that sertraline may be a better choice for patients exhibiting psychomotor agitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute antidepressant response to fluoxetine and sertraline in psychiatric outpatients with psychomotor agitation. Lane, MF.[2014]

The study developed a self-micro emulsifying drug delivery system (SMEDDS) to enhance the solubility and oral bioavailability of sertraline, which typically has a low bioavailability of 44%.

The optimized formulation (batch A3) demonstrated excellent stability and significant in-vitro antidepressant action, with a drug release of 98.25% within 8 hours and a globule size of 101 nm, indicating its potential for improved therapeutic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation and Characterization of Self-Microemulsifying Drug Delivery System (SMEDDS) of Sertraline Hydrochloride. Sharma, S., Kanugo, A., Kaur, T., et al.[2022]

Sertraline, a commonly used antidepressant, is generally considered safe but can cause side effects like nausea, insomnia, and dizziness, which were also experienced by the patient in this case report.

In a rare instance, a patient developed sinus arrest just four days after starting sertraline treatment, highlighting the need for careful monitoring of cardiac symptoms when prescribing this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sinus arrest due to sertraline. Kocabay, G., Yildiz, M., Eksi Duran, N., et al.[2022]

In a study involving 1251 patients, sertraline was found to have a similar safety profile to other SSRIs, with common side effects like nausea, headache, and diarrhea reported by both groups.

Despite the similarities, sertraline users reported a higher incidence of diarrhea compared to users of other SSRIs, and the study identified over 100 different unlabelled adverse events, indicating the need for ongoing monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. Meijer, WE., Heerdink, ER., van Eijk, JT., et al.[2022]

Azithromycin (AZM) demonstrated a high clinical efficacy rate of 92.2% in treating infectious diseases in children, with a notable 94.0% efficacy in patients who had previously failed other treatments, based on an evaluation of 564 cases.

The safety profile of AZM was favorable, with only 2.5% of patients experiencing mild to moderate adverse reactions, such as diarrhea and skin rashes, which were transient and resolved without long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical studies with azithromycin (fine granule) in the pediatric field. Pediatric Study Group of Azithromycin]. Tajima, T., Kobayashi, M., Terashima, I., et al.[2016]

Single-dose azithromycin (30 mg/kg) demonstrated a high clinical success rate of 88% in treating children with otitis media, based on data from four clinical trials involving 619 patients.

The treatment was found to be safe, with mostly mild and temporary side effects, and showed excellent compliance rates of 99-100%, making it a suitable alternative for pediatric patients, especially in areas with low macrolide resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose azithromycin for the treatment of children with acute otitis media. Soley, CA., Arguedas, A.[2006]

In a study of 410 patients with severe watery diarrhea, including 316 with cholera, chlorpromazine significantly reduced oral therapy failure rates by about 50% in children with severe cholera, particularly those presenting with shock or high purging rates.

However, chlorpromazine did not show significant benefits in adults with cholera or patients with noncholera diarrhea, leading to the conclusion that it should not be routinely used for watery diarrhea management, but may be beneficial for severe cases in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of chlorpromazine in the treatment of cholera and other severe acute watery diarrheal diseases. Islam, MR., Sack, DA., Holmgren, J., et al.[2013]

A single dose of Azithromycin (1 gram) was found to be as effective as Norfloxacin (400 mg twice daily for three days) in treating cholera in adults, based on a study of 64 patients with confirmed Vibrio cholerae infection.

Both treatments effectively reduced stool output, duration of diarrhea, and fluid requirements, indicating that Azithromycin is a viable alternative to Norfloxacin for cholera management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between Single Dose Azithromycin and Six Doses, 3 Day Norfloxacin for Treatment of Cholera in Adult. Bhattacharya, MK., Kanungo, S., Ramamurthy, T., et al.[2020]

In a study involving 594 patients treated for uncomplicated gonorrhoea, the 2 g split dose of azithromycin resulted in significantly fewer gastrointestinal side effects, such as vomiting, nausea, and diarrhea, compared to the 2 g single dose.

The 1 g single dose of azithromycin was associated with even lower rates of these side effects, making it a preferable option for patients, with a high willingness (97%) to retake the same dosing in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of gastrointestinal side effects from different doses of azithromycin for the treatment of gonorrhoea. Ong, JJ., Aguirre, I., Unemo, M., et al.[2022]

References

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

Sertraline effects in adolescent major depression and dysthymia: a six-month open trial. [2013]

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

Coadministration of sertraline with cisapride or pimozide: an open-label, nonrandomized examination of pharmacokinetics and corrected QT intervals in healthy adult volunteers. [2022]

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

Pediatric sertraline overdose. [2022]

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

Sertraline: a new specific serotonin reuptake blocker. [2019]

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

Acute antidepressant response to fluoxetine and sertraline in psychiatric outpatients with psychomotor agitation. [2014]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Formulation and Characterization of Self-Microemulsifying Drug Delivery System (SMEDDS) of Sertraline Hydrochloride. [2022]

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

Sinus arrest due to sertraline. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical studies with azithromycin (fine granule) in the pediatric field. Pediatric Study Group of Azithromycin]. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Single-dose azithromycin for the treatment of children with acute otitis media. [2006]

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

The use of chlorpromazine in the treatment of cholera and other severe acute watery diarrheal diseases. [2013]

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

Comparison between Single Dose Azithromycin and Six Doses, 3 Day Norfloxacin for Treatment of Cholera in Adult. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Comparison of gastrointestinal side effects from different doses of azithromycin for the treatment of gonorrhoea. [2022]