Sertraline for Anxiety in Neurodevelopmental Disorders

(CALM Trial)

Recruiting at 8 trial locations

Overseen By Evdokia Anagnostou

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Anagnostou, Evdokia, M.D.

Must not be taking: SSRIs, MAOIs, Pimozide, others

Disqualifiers: Diabetes, HIV, Hepatitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether sertraline, a medication commonly used for anxiety, can reduce anxiety in children and teens with neurodevelopmental disorders such as autism or ADHD. The researchers aim to compare the effectiveness of sertraline to a placebo and determine the best methods for measuring anxiety improvements in future studies. Children and teens aged 8-17 with a diagnosed neurodevelopmental disorder and an anxiety disorder who can communicate in phrases may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important early findings.

Will I have to stop taking my current medications?

If you are taking medications that affect behavior, you must be on a stable dose for at least a month before the trial and cannot change them during the study. You cannot be on other SSRIs (a type of antidepressant) within four weeks of starting the trial, and certain other medications are also not allowed. The protocol does not specify a complete stop of all current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sertraline is generally well-tolerated in children and teens with anxiety, though it has not been extensively studied in those with neurodevelopmental disorders (NDDs). In general use, sertraline reduces anxiety symptoms and improves mental health within weeks. While approved for certain conditions in children, such as obsessive-compulsive disorder (OCD), its safety for other uses in young people remains under investigation.

When taken in typical doses, sertraline usually causes mild side effects. Common side effects may include an upset stomach or trouble sleeping, which often improve over time. One study found that even higher doses are safe and do not significantly increase side effects.

However, because this trial is in an early phase, the full safety profile in children with NDDs is still being determined. Researchers carefully monitor participants in such trials to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about sertraline for anxiety in neurodevelopmental disorders because it offers a unique approach compared to current treatments. Most treatments for anxiety, especially within neurodevelopmental disorders, focus on therapies like cognitive-behavioral therapy or medications such as benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) specifically approved for anxiety. However, sertraline is already known as an SSRI used for depression and anxiety in the general population, but its use in neurodevelopmental disorders is still being explored. Sertraline's potential lies in its ability to specifically adjust serotonin levels, which might address anxiety symptoms effectively in individuals with neurodevelopmental disorders, potentially offering a more targeted and effective treatment option. Researchers hope it could lead to improved management of anxiety symptoms in this specific group, providing benefits over existing treatments.

What evidence suggests that sertraline might be an effective treatment for anxiety in neurodevelopmental disorders?

Research has shown that sertraline, which participants in this trial may receive, can help reduce anxiety symptoms. In studies with children and teens, it led to noticeable improvements in anxiety within six weeks. While often used to treat anxiety in young people, more information is needed about its effects on those with neurodevelopmental disorders (NDDs). In adults, sertraline effectively treats social anxiety and has shown good results in children with obsessive-compulsive disorder. Although strong evidence supports its use for general anxiety, further research is needed to confirm its benefits for anxiety in people with NDDs. ^{1 3 6 7 8}

Who Is on the Research Team?

Dr. Evdokia Anagnostou

Principal Investigator

Holland Bloorview Kids Rehab Hospital

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 8-17 with neurodevelopmental disorders like ASD, ADHD, or genetic conditions such as Fragile X syndrome. They must have anxiety symptoms and be able to communicate in English/French. Participants should not have had more than two unsuccessful SSRI treatments or any previous adverse reactions to sertraline.

Inclusion Criteria

You are moderately ill based on a clinician's assessment of your anxiety.

I can complete assessments in English or French.

I have been diagnosed with an anxiety disorder like separation, social anxiety, or agoraphobia.

Exclusion Criteria

I've tried at least two SSRIs without success.

I do not have any serious health issues that could affect the study or my safety, and I am not on diabetes medication.

I have a known genetic heart condition that affects my heart's rhythm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sertraline or placebo to assess the effect on anxiety in children and adolescents with neurodevelopmental disorders

16 weeks

Regular visits for assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sertraline

Trial Overview The study tests Sertraline, a medication thought to help with anxiety, against a placebo in kids with various neurodevelopmental issues. It aims to find out how effective Sertraline is and identify the best ways to measure its impact on anxiety across different conditions.

How Is the Trial Designed?

Group I: Sertraline Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Anagnostou, Evdokia, M.D.

Lead Sponsor

Trials

3

Recruited

180+

Holland Bloorview Kids Rehabilitation Hospital

Lead Sponsor

Trials

69

Recruited

14,100+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Dalhousie University

Collaborator

Trials

177

Recruited

402,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

St. Justine's Hospital

Collaborator

Trials

205

Recruited

87,300+

Azrieli Foundation

Collaborator

Trials

1

Recruited

130+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Ontario Brain Institute

Collaborator

Trials

12

Recruited

3,000+

Published Research Related to This Trial

Sertraline is an effective and well-tolerated treatment for various anxiety disorders, including panic disorder and obsessive-compulsive disorder, based on extensive research from controlled and open trials.

When compared to other medications for anxiety disorders, sertraline demonstrates at least equivalent efficacy, making it a viable option for patients seeking treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline in the treatment of anxiety disorders. Hirschfeld, RM.[2022]

In a 12-week open trial of sertraline involving 22 patients with Social Phobia, 80% of participants responded positively to the treatment after at least 8 weeks.

Statistically significant improvements were observed in social anxiety, avoidance, depression, and social functioning from the beginning to the end of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline in social phobia. Van Ameringen, M., Mancini, C., Streiner, D.[2019]

In a study involving 72 children aged 6-18, sertraline (Zoloft) was found to be very effective and safe for treating depression, anxiety, and obsessive-compulsive disorders over an 8-week period.

The medication showed quick thymoanaleptic (mood-lifting) and anxiolytic (anxiety-reducing) effects, with a significant dose of 50 mg/day for mild depression and up to 100 mg/day for more severe cases, without impacting cognitive functions or causing sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sertraline in child and adolescent psychiatry]. Voloshina, VM., Kashnikova, AA., Tatarova, IN., et al.[2022]

In a combined analysis of two multicenter clinical trials, sertraline significantly reduced the mean number of panic attacks per week in patients with panic disorder compared to placebo (4.8 vs. 2.5, p < .001).

Patients treated with sertraline also showed statistically significant improvements in various symptoms and functioning related to panic disorder, highlighting its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodologies and outcomes from the sertraline multicenter flexible-dose trials. Rapaport, MH., Wolkow, RM., Clary, CM.[2013]

In a study involving 619 participants with generalized social anxiety disorder (SAD), treatment with sertraline significantly improved symptoms across all dimensions of the Brief Social Phobia Scale, including fear, avoidance, and physiological arousal.

Specifically, sertraline was particularly effective in reducing physiological symptoms like blushing and palpitations, while its effects on trembling and sweating were less pronounced, highlighting the varied responsiveness of different symptoms to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidimensional effects of sertraline in social anxiety disorder. Connor, KM., Davidson, JR., Chung, H., et al.[2022]

In a study of 178 out-patients with panic disorder, sertraline significantly reduced the frequency of panic attacks and anxiety symptoms compared to placebo over 12 weeks, demonstrating its efficacy in treating panic disorder.

Sertraline was found to be safe, with no serious adverse events reported, although some patients experienced mild side effects like dry mouth and ejaculation issues, and higher doses did not provide additional benefits over the 50 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigation. Londborg, PD., Wolkow, R., Smith, WT., et al.[2022]

In an 8-week open-label study of 14 children with social anxiety disorder, sertraline led to significant improvements in anxiety symptoms, with 36% of participants classified as treatment responders by the end of the trial.

Sertraline was generally well tolerated, and significant clinical responses were observed by week 6, indicating its potential as an effective treatment for childhood social anxiety disorder, warranting further rigorous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline in children and adolescents with social anxiety disorder: an open trial. Compton, SN., Grant, PJ., Chrisman, AK., et al.[2013]

In a study involving 22 children and adolescents aged 5-17 with generalized anxiety disorder, sertraline was found to be significantly more effective than placebo, with improvements noted as early as week 4.

The study concluded that a daily dose of 50 mg of sertraline is both safe and effective for treating generalized anxiety disorder in this age group, as measured by the Hamilton Anxiety Rating Scale and Clinical Global Impression scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Rynn, MA., Siqueland, L., Rickels, K.[2022]

In a study of 488 anxious youth aged 7-17, those receiving a combination of sertraline and cognitive behavioral therapy (COMB) had the highest remission rates (46% to 68%) compared to other treatments, indicating that combining medication with therapy is the most effective approach.

While both sertraline and cognitive behavioral therapy showed better remission rates than placebo, many participants still experienced persistent anxiety symptoms after 12 weeks, highlighting the need for ongoing treatment strategies for some children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission after acute treatment in children and adolescents with anxiety disorders: findings from the CAMS. Ginsburg, GS., Kendall, PC., Sakolsky, D., et al.[2022]

Sertraline is a well-tolerated selective serotonin reuptake inhibitor that effectively treats various depressive and anxiety disorders, showing efficacy even in patients with psychiatric and medical comorbidities.

It is effective for both short-term and long-term management of conditions like major depressive disorder, social anxiety disorder, PTSD, panic disorder, generalized anxiety disorder, and OCD, with a low risk of fatal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. Sheehan, DV., Kamijima, K.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7029306/

The clinical effectiveness of sertraline in primary care and the ... Sertraline leads to reduced anxiety symptoms and self-reported improvements in mental health within 6 weeks, but any effect on depressive ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4655145/

Long Term Sertraline Effects on Neural Structures in ... Sertraline reduced anxiety (p=0.04) but not depressive behavior (p=0.43). Left Brodmann's Area (BA)32 was smaller in depressed than nondepressed monkeys (main ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06081348

Sertraline vs. Placebo in the Treatment of Anxiety ... Sertraline, a selective serotonin reuptake inhibitor, has extensive evidence to support its use in children's and youth with anxiety but not within NDDs.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2009/019839s070,020990s032lbl.pdf

ZOLOFT - accessdata.fda.gov The efficacy of ZOLOFT in the treatment of social anxiety disorder was established in two placebo-controlled trials of adult outpatients with a diagnosis of ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/188200

Sertraline in Children and Adolescents With Obsessive ... Conclusion.— Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK547689/

Sertraline - StatPearls - NCBI Bookshelf - NIH Sertraline is a medication used to manage and treat the major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress ...

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

ZOLOFT (sertraline hydrochloride) Label - accessdata.fda.gov Safety and effectiveness have not been established in pediatric patients for indications other than OCD. Two placebo-controlled trials were conducted in ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0010440X24000373

Off-label higher doses of serotonin reuptake inhibitors in ... OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.