Sertraline for PTSD

(SSRI Trial)

No longer recruiting at 1 trial location

Overseen By Ann Rasmusson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must be taking: SSRIs

Must not be taking: SNRIs, Antipsychotics

Disqualifiers: Bipolar, Schizophrenia, Pregnancy, others

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: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and reliability of a quick screening method for predicting which individuals with posttraumatic stress disorder (PTSD) or depression respond well to SSRIs. The study will compare the effects of the medication sertraline (Zoloft) against a placebo to determine which is more effective. Individuals who have experienced trauma and have been diagnosed with PTSD or depression may be suitable candidates if they are interested in trying an SSRI. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial requires that you have not used SSRIs or drugs affecting the serotonin system for 3 months before starting. Other psychotropic medications must be stable for 3 months before and during the study.

What is the safety track record for sertraline?

Research has shown that sertraline is a safe and effective treatment for posttraumatic stress disorder (PTSD). Studies have consistently found that it benefits many people with PTSD. The data suggest that sertraline has few side effects, and most patients tolerate it well without major issues.

Sertraline is a type of antidepressant called an SSRI. The FDA has already approved it to treat PTSD, depression, and anxiety, indicating thorough safety testing. While some people might experience mild side effects, such as an upset stomach or trouble sleeping, these are usually not serious.

In past research, sertraline helped many people with PTSD feel better, making it a reliable treatment option. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about sertraline for PTSD because it offers a flexible dosing strategy that can be tailored to each individual's response and tolerance. Unlike standard treatments like cognitive behavioral therapy or other medications, sertraline allows for adjustments in dosage based on how well a person is responding, potentially minimizing side effects. This personalized approach could lead to better outcomes for those who haven't found relief with existing options.

What is the effectiveness track record for sertraline in treating PTSD?

Research has shown that sertraline can help treat posttraumatic stress disorder (PTSD). In this trial, participants will be divided into two groups: one will receive sertraline, while the other will receive a placebo. Some studies found that people taking sertraline experienced noticeable improvements compared to those taking a placebo, which contains no active medicine. Sertraline was particularly effective at reducing certain PTSD symptoms. It is also considered safe and generally well-tolerated by patients. Overall, strong evidence supports that sertraline can help people with PTSD feel better. ^{2 3 5 6 7}

Who Is on the Research Team?

Suzanne Pineles, PhD

Principal Investigator

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Are You a Good Fit for This Trial?

This trial is for veterans with PTSD or major depression who've experienced trauma, meet DSM-5 criteria for these conditions, and are open to trying SSRI medication. They shouldn't have a severe substance use disorder, be at immediate risk of harm to self or others, have used certain serotonin-affecting drugs recently, be pregnant, or currently in specific psychotherapies.

Inclusion Criteria

I am interested in trying an SSRI medication.

A psychiatrist agrees SSRIs are suitable for my mental health issues.

I have been diagnosed with PTSD, subthreshold PTSD, or major depression.

Exclusion Criteria

Pregnancy

I do not have any severe liver, kidney, or other unstable health conditions.

I have significant issues with my nervous system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Placebo Lead-in

Participants undergo a 2-week placebo lead-in phase to identify placebo responders

2 weeks

1 visit (in-person)

Treatment

Placebo non-responders receive sertraline, with dose adjustments based on clinical response and tolerability

12 weeks

Bi-weekly visits (in-person) with psychiatrist check-ins

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sertraline

Trial Overview The study tests if a brief screening can predict positive responses to SSRIs in those with PTSD or depression. Participants will either receive the SSRI sertraline or a placebo over 17 weeks to assess the effectiveness of this prediction method.

How Is the Trial Designed?

Group I: Sertraline arm Active Control 3 Interventions

After the 2-week placebo lead-in phase, placebo-non responders will receive sertraline 25 mg daily for 2 weeks. Thereafter, sertraline will be increased flexibly by 25 to 50 mg per day (at a rate no higher than 50 mg per week) to achieve a total daily dose of 50 to 200 mg, based on clinical response and tolerability, with a maximum dose of 200 mg/d. Subjects unable to tolerate higher doses may be dropped back to the previous dose and remain at that dose for the remainder of the study.

Group II: Placebo only arm Placebo Group 2 Interventions

For individuals who are placebo responders during the 2 week placebo lead in phase, they will remain on placebo for the duration of the study (i.e., the 12 weeks where the placebo non-responders are taking sertraline).

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Middlebury College

Collaborator

Trials

1

Recruited

90+

Ralph H. Johnson VA Medical Center

Collaborator

Trials

21

Recruited

5,700+

Published Research Related to This Trial

In a study of 122 Japanese patients with PTSD treated with sertraline for an average of 10.6 months, 50% were considered responders, and 65.6% showed improvement in PTSD severity, indicating sertraline's effectiveness in this population.

The safety profile of sertraline was consistent with known data, with no serious adverse events reported, suggesting it is a safe option for treating PTSD in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosage, effectiveness, and safety of sertraline treatment for posttraumatic stress disorder in a Japanese clinical setting: a retrospective study. Kamo, T., Maeda, M., Oe, M., et al.[2022]

In a study involving 72 Chinese patients with PTSD, sertraline (135 mg daily) was found to be effective in improving PTSD symptoms over 12 weeks, as measured by the Impact of Event Scale-Revised and Clinical Global Impression Scale-Severity scores.

The treatment was generally well-tolerated, with nausea being the most common side effect reported in 33.3% of the sertraline group, but no serious adverse events or deaths were associated with the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and safety of sertraline for treat posttraumatic stress disorder: a multicenter randomised controlled study. Li, W., Ma, YB., Yang, Q., et al.[2022]

In a pilot study involving 42 Israeli military veterans with PTSD, sertraline showed a numeric advantage over placebo in reducing PTSD symptoms, although this was not statistically significant in the overall analysis.

Sertraline was well tolerated with a low discontinuation rate of 13% due to adverse events, suggesting it may be a viable treatment option for combat-induced PTSD, but further studies are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder. Zohar, J., Amital, D., Miodownik, C., et al.[2019]

In a study of 395 PTSD patients, sertraline was found to be effective and well tolerated, significantly improving PTSD symptoms compared to placebo, regardless of whether patients had comorbid anxiety or depression.

Patients with both depression and anxiety disorders showed the highest severity of PTSD symptoms at baseline and benefited from slightly higher doses of sertraline, indicating that comorbidity may influence treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Affective and anxiety comorbidity in post-traumatic stress disorder treatment trials of sertraline. Brady, KT., Clary, CM.[2015]

In a study of 131 children and adolescents with PTSD, sertraline was found to be generally safe, with a higher dropout rate due to adverse events compared to placebo (29.9% vs. 17.7%).

However, sertraline did not show significant efficacy in reducing PTSD symptoms compared to placebo over the 10-week treatment period, indicating it may not be an effective treatment option for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline treatment of children and adolescents with posttraumatic stress disorder: a double-blind, placebo-controlled trial. Robb, AS., Cueva, JE., Sporn, J., et al.[2022]

Sertraline is an effective treatment for post-traumatic stress disorder (PTSD), offering advantages over older antidepressants, including better tolerability and a lower risk of overdose lethality.

Due to its efficacy, favorable side effect profile, and minimal interaction with the cytochrome P450 system, sertraline is recommended as a first-line treatment option for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of sertraline in post-traumatic stress disorder. Schwartz, AC., Rothbaum, BO.[2022]

In a study analyzing two 12-week placebo-controlled trials, sertraline was found to be effective in treating 15 out of 17 PTSD symptoms, particularly those related to numbing and hyperarousal.

The treatment showed a significant early effect on anger from the first week, which helped explain improvements in other PTSD symptoms over time, with notable responses observed by weeks 6 and 10.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing the effects of sertraline in post-traumatic stress disorder. Davidson, JR., Landerman, LR., Farfel, GM., et al.[2019]

In a study of 36 adults with PTSD, combining sertraline (an SSRI) with mirtazapine resulted in a significantly higher remission rate and greater improvement in depressive symptoms compared to sertraline plus placebo over 24 weeks.

Both treatment options were well-tolerated, with the combined treatment showing some increased appetite but no significant weight gain, suggesting it may be a viable option for improving symptoms in PTSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COMBINED MIRTAZAPINE AND SSRI TREATMENT OF PTSD: A PLACEBO-CONTROLLED TRIAL. Schneier, FR., Campeas, R., Carcamo, J., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10770145/

Efficacy and safety of sertraline treatment of posttraumatic ... Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end ...

2. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2716980

Efficacy of Prolonged Exposure Therapy, Sertraline ... Meaning No difference in change in posttraumatic stress disorder symptoms or symptom severity at 24 weeks was found across the 3 groups of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6439753/

Efficacy of Prolonged Exposure Therapy, Sertraline ... No difference in change in posttraumatic stress disorder symptoms or symptom severity at 24 weeks was found across the 3 groups of sertraline ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/192575

Efficacy and Safety of Sertraline Treatment of Posttraumatic ... Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD. Traumatic stress is a significant public health problem.

5. apa.org apa.org/ptsd-guideline/treatments/eficacy-sertraline-ptsd.pdf

Efficacy and Safety of Sertraline Treatment of Posttraumatic ... Post- traumatic stress disorder and functioning and quality of life outcomes in a nationally representative sample of male Vietnam veterans. Am J Psychiatry.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/019839s74s86s87_20990s35s44s45lbl.pdf

ZOLOFT (sertraline hydrochloride) Label - accessdata.fda.gov • Panic disorder (PD). • Post-traumatic stress disorder (PTSD). • Social anxiety disorder (SAD). • Premenstrual dysphoric disorder (PMDD). --------------------- ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/sertraline-oral-route/description/drg-20065940

Sertraline (oral route) - Side effects & dosage Sertraline is used to treat depression, obsessive-compulsive disorder ... posttraumatic stress disorder (PTSD), and social anxiety disorder (SAD).