Sertraline for Anxiety in Neurodevelopmental Disorders

(CALM Trial)

Recruiting at 7 trial locations

Overseen By Faiza Khawaja

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Anagnostou, Evdokia, M.D.

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

Disqualifiers: Diabetes, HIV, Hepatitis, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

There are currently no approved medications for the treatment of anxiety in children and youth with neurodevelopmental disorders (NDDs), both common and rare. Sertraline, a selective serotonin reuptake inhibitor, has extensive evidence to support its use in children's and youth with anxiety but not within NDDs. More research is needed to confirm whether or not sertraline could help improve anxiety in children and youth with common and rare neurodevelopmental conditions. This is a pilot study, in which we plan to estimate the effect size of reduction in anxiety of sertraline vs. placebo. across rare and common neurodevelopmental disorders, and determine the best measure(s) to be used as a primary transdiagnostic outcome measure of anxiety, as well as diagnosis specific measures in future, larger-scale clinical trials of anxiety in NDDs.

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.

What data supports the effectiveness of the drug sertraline for anxiety in neurodevelopmental disorders?

Research shows that sertraline, a drug used to treat anxiety, has been effective in reducing symptoms of social anxiety and panic disorder in adults, as well as generalized anxiety disorder in children. In these studies, patients taking sertraline experienced significant improvements compared to those taking a placebo (a dummy treatment with no active drug). ^{1 2 3 4 5}

Is sertraline safe for humans?

Sertraline, also known as Zoloft, has been studied extensively and is generally considered safe and well-tolerated in both adults and children for various conditions, including anxiety and mood disorders. It has a good safety profile with low risk of serious side effects. ^{2 3 6 7 8}

How does the drug sertraline differ from other treatments for anxiety in neurodevelopmental disorders?

Sertraline is unique because it has been extensively tested and shown to be effective for various anxiety disorders, including panic and obsessive-compulsive disorders, and is well-tolerated in children without affecting cognitive functions. This makes it a promising option for anxiety in neurodevelopmental disorders, where standard treatments may not be well-established. ^{1 2 8 9 10}

Research Team

Evdokia Anagnostou, MD

Principal Investigator

Holland Bloorview Kids Rehab Hospital

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Other)
• Sertraline (Selective Serotonin Reuptake Inhibitor)

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.

Participant Groups

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+

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+

Holland Bloorview Kids Rehabilitation Hospital

Collaborator

Trials

69

Recruited

14,100+

Findings from Research

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 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 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 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 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]

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]

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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Sertraline in social phobia. [2019]

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

Methodologies and outcomes from the sertraline multicenter flexible-dose trials. [2013]

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

Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. [2022]

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

Multidimensional effects of sertraline in social anxiety disorder. [2022]

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

Remission after acute treatment in children and adolescents with anxiety disorders: findings from the CAMS. [2022]

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

Sertraline in children and adolescents with social anxiety disorder: an open trial. [2013]

7. England pubmed.ncbi.nlm.nih.gov

An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. [2022]

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

Sertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigation. [2022]

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

Sertraline in the treatment of anxiety disorders. [2022]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Sertraline in child and adolescent psychiatry]. [2022]