Azithromycin for Acute-Onset Obsessive-Compulsive Disorder in Children
The Carlat Child Psychiatry Report, Volume 9, Number 2&3, March 2018
Thomas Jordan, MD
Dr. Jordan has disclosed that he has no relevant financial or other interests in any commercial companies pertaining to this educational activity.
Review of: Murphy et al, J Child Adolesc Psychopharmacol 2017; 27(7):640–651
Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric syndrome associated with streptococcus (PANDAS) have been the subject of many debates in the field.
From obsessions, compulsions, and tics, to personality changes and oppositional behavior, the symptoms of PANS are wide-ranging. PANDAS is considered a subset of PANS that is temporally associated with a Group A streptococcal (GAS) infection.
Due to the link to an infectious cause, antibiotics are being assessed as a treatment for PANS. This study specifically evaluated the tolerability and efficacy of azithromycin in treating children with acute onset of OCD who met criteria for PANS.
Conducted with 31 children ages 4–14, the study was a randomized, double-blind, placebo-controlled trial comparing treatment with azithromycin (10 mg/kg, up to 500 mg per day) to placebo for children with an acute onset of moderate or worse OCD symptoms and neuropsychiatric symptoms. The primary outcomes were changes in the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and in the Clinical Global Impression—Severity (CGI-S) scale. Several secondary outcomes were measured, including other scales for tic severity, affective lability, and anxiety. Outcome measurements were taken at baseline and then weekly for four weeks over the study period.
The results of the trial were split. The azithromycin group had a significantly greater reduction in OCD severity as measured by the CGI-S (p = 0.003) at week 4, but there was no significant difference between the treatment and control groups in the CY-BOCS scores (p = 0.203). Interestingly, the children in the azithromycin group with greater tic severity at baseline showed the most improvement in the CGI-S. For the secondary outcome measures, the only significant effect was a reduction in the Clinical Global Impression—Improvement Mood subscale (p = 0.006) in the azithromycin group.
As for side effects, the azithromycin group had significantly more loose stools (53% of treatment group vs 7% of placebo group), and the placebo group reported more constipation (36% of placebo group vs 0% of treatment group). Electrocardiograms were monitored at baseline and at week 4, showing a significant increase in the QTc (p = 0.007) for children in the azithromycin group. Four participants in the azithromycin group had a borderline QTc of 440–460 at week 4 versus 1 participant in the placebo group.
This study, along with other past trials of antibiotics for PANS, gives us mixed results. The authors postulate that the CY-BOCS may not have been the best rating tool for the younger children in this trial, leading to the less robust results compared to the CGI-S outcome. Better response to antibiotic treatment was mediated by baseline tic severity, which will need further exploration. The authors also recognize the limitations of the small study size, and view this as a pilot study that may lead to larger trials in the future. If you do embark on using azithromycin, consider baseline and follow-up electrocardiograms to watch for QTc changes.