Dr. Kumar’s Take:
This study from the National Institute of Mental Health tested whether preventing strep infections would reduce neuropsychiatric flares in children with PANDAS. Two points about the design matter before the results: it was a small trial of 23 children, and it had no placebo arm. Every child received an antibiotic, either penicillin or azithromycin, and the comparison was each child’s study year against the year before they enrolled. Both infections and symptom exacerbations dropped significantly on that comparison. I read that as encouraging but not conclusive, because a design without a placebo group cannot separate the drug’s effect from the natural tendency of these symptoms to settle over time. For a child with a clear, documented pattern of flares following strep, this supports discussing prophylaxis as part of a closely monitored plan.
Key Takeaways:
✔ 23 children with PANDAS received antibiotic prophylaxis for 12 months.
✔ 11 children were assigned penicillin and 12 were assigned azithromycin.
✔ Strep infections fell to a mean of 0.1 per child during the study year, from 1.9 in the penicillin group and 2.4 in the azithromycin group during the baseline year.
✔ Neuropsychiatric exacerbations fell significantly during the study year, from a baseline mean of 2.0 per child in the penicillin group and 1.8 in the azithromycin group.
✔ Throat cultures, antibody titers and symptom ratings were collected monthly, and any child with a confirmed strep infection came off the study drug for a 10 day course of a different class of antibiotic.
Actionable tip:
If your child’s OCD or tics tend to worsen after confirmed strep infections, talk to your doctor about whether antibiotic prevention during high-risk periods, such as a strep outbreak at school, makes sense for them.
Brief Summary:
This double blind, randomized trial followed 23 children diagnosed with PANDAS, a condition in which strep infections are linked to sudden-onset OCD or tics. Children were randomly assigned to penicillin or azithromycin for 12 months, and their rates of strep infection and neuropsychiatric exacerbation were compared against the year before they entered the study. Strep infections dropped to a mean of 0.1 per child, down from 1.9 in the penicillin group and 2.4 in the azithromycin group at baseline. Neuropsychiatric exacerbations also dropped significantly, down from a baseline mean of 2.0 per child on penicillin and 1.8 on azithromycin. Both changes reached statistical significance at p less than .01. The authors concluded that both drugs were effective at reducing strep infections and neuropsychiatric symptom exacerbations in this subgroup.
Study Design:
- Type: Randomized, double blind trial comparing two antibiotics, with each child’s study year measured against their own baseline year
- Participants: 23 children, mean age 7.9 years, range 5.3 to 9.8 years, 15 boys and 8 girls, all with a tic disorder and/or OCD, symptom onset before puberty, and a documented temporal link between strep infection and symptom onset or exacerbation
- Diagnoses: OCD only in 9 children, OCD with a tic disorder in 7, tic disorder with subclinical OCD in 4, tic disorder only in 3
- Groups:
- Penicillin V-K: 250 mg twice daily
- Azithromycin: 250 mg twice daily on one day of the week, with placebo capsules twice daily on the other six days
- Duration: 12 months
- Monitoring: Monthly throat cultures, antistreptolysin O and anti-DNase B titers, and monthly symptom ratings using the CY-BOCS and YGTSS scales
- Compliance: Identical blinded capsules in blister packs labeled by day and by AM or PM, returned monthly for pill counts, with parents also reporting missed doses on a written form
Results:
- Strep infections: Mean of 0.1 per child during the study year, compared with 1.9 in the penicillin group and 2.4 in the azithromycin group during the baseline year, p less than .01
- Neuropsychiatric symptom exacerbations: Significant decrease during the study year, compared with a mean of 2.0 per child in the penicillin group and 1.8 in the azithromycin group at baseline, p less than .01
- Breakthrough infections: Children with a confirmed strep infection stopped the study drug, took a 10 day course of an antibiotic outside the penicillin and macrolide classes, then resumed the study drug
- Baseline status: Every child had a negative throat culture before randomization
How Do Antibiotics Help in PANDAS?
The theory behind prophylactic antibiotics in PANDAS is straightforward: if you can prevent strep infections, you may stop the immune reaction that drives the OCD or tic symptoms. The same logic underpins penicillin prophylaxis in rheumatic fever, which is where the researchers borrowed the idea from. This study found that infections and symptom flares fell together, which is what that model predicts. Proving the link will take a trial with a genuine placebo group.
Related Studies and Research
PANS and Corticosteroids: A Study Review Reviews outcomes of corticosteroid use during PANS flares.
Plasma Apheresis for Severe PANDAS Symptoms Analyzes therapeutic plasma exchange in children with severe PANDAS.
PANDAS OCD Treatment Overview Summarizes current treatment strategies for PANDAS-related OCD.
Podcast: Could Your Child’s Behavior Changes Be Cured with an Antibiotic? A deep dive into the link between strep infections and dramatic neuropsychiatric symptoms.
Frequently Asked Questions
Why were two antibiotics tested?
An earlier trial at the same center found that oral penicillin failed to prevent strep infections adequately, so the researchers expected penicillin to act as a weak comparison drug and azithromycin to prevent infections more completely. Families were told during consent that they might receive the less effective drug.
Were kids taken off the study drugs if they got strep?
Yes. A child with a confirmed strep infection stopped the study drug, took a 10 day course of an antibiotic from a different class, then went back on the study drug.
Did the antibiotics improve OCD or tic symptoms directly?
No. The antibiotics were given to prevent strep infections. The premise was that fewer infections would mean fewer psychiatric flares, and the exacerbation counts did fall alongside the infection counts.
Should all kids with PANDAS be on antibiotics year-round?
Not on the strength of this trial. It enrolled 23 children and had no placebo group, so it is a case-by-case decision to make with a physician who knows the condition.
Conclusion
Both penicillin and azithromycin cut strep infections and neuropsychiatric exacerbations in these 23 children over 12 months, and the authors concluded that both drugs were effective in this subgroup. The size of the trial and the absence of a placebo arm mean the finding needs confirmation before it becomes routine practice. If your child shows a clear pattern of flares after confirmed strep, bring this study to your pediatrician or a specialist and ask whether a prevention strategy fits their history.
