title: A Double-Blind Randomized Placebo-Controlled Pilot Study of Azithromycin in Youth with Acute-Onset Obsessive-Compulsive Disorder.
abstract: OBJECTIVE
  Sudden and severe onset of obsessive-compulsive disorder (OCD) may present secondary to infectious and/or immune-mediated triggers. We assessed the preliminary efficacy, tolerability, and safety of azithromycin compared with placebo in the treatment of OCD and associated symptoms in children with pediatric acute-onset neuropsychiatric syndrome (PANS).
  
  
  METHODS
  Thirty-one youth aged 4-14 years (M = 8.26 ± 2.78 years, 62.5% male) were randomized to receive either placebo or azithromycin for 4 weeks (10 mg/kg up to 500 mg per day). Both groups were administered twice daily probiotics. The primary outcome, obsessive-compulsive symptom severity, was assessed using the OCD Clinical Global Impressions Severity (CGI-S OCD) and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS).
  
  
  RESULTS
  Participants in the azithromycin group (n = 17) showed significantly greater reductions in OCD severity on the CGI-S OCD than the placebo group (n = 14) posttreatment (p = 0.003), although there were no significant differences on the CY-BOCS. Significantly more participants in the azithromycin condition met treatment responder criteria on the CGI-I OCD at the end of week 4 (41.2%, n = 7) in comparison to the placebo group (7.1%, n = 1; p = 0.045). Tic severity moderated treatment response, with greater tic severity being associated with enhanced treatment response on the CGI-S OCD. Azithromycin was well tolerated with minimal adverse effects and no study dropouts due to side effects. However, the azithromycin group showed a trend toward significantly greater electrocardiography QTc (p = 0.060) at the end of week 4, and significantly more reports of loose or abnormal stools (p = 0.009).
  
  
  CONCLUSIONS
  This double blind pilot study suggests that azithromycin may be helpful in treating youth meeting the PANS diagnosis, especially those with elevated levels of both OCD and tic symptoms. Azithromycin was well tolerated, but the potential for cardiac risks suggests that additional monitoring may be needed to ensure safety.
authors.affiliation: 1 Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida , St. Petersburg, Florida.|2 Department of Psychiatry & Behavioral Sciences, University of South Florida , St. Petersburg, Florida.|3 All Children's Hospital-Johns Hopkins Medicine , St. Petersburg, Florida.
authors.forename: Tanya K
authors.initials: TK
authors.lastname: Murphy
authors.affiliation: 1 Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida , St. Petersburg, Florida.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Brennan
authors.affiliation: 4 Department of Psychology-Macquarie University , Sydney, New South Wales.
authors.forename: Carly
authors.initials: C
authors.lastname: Johnco
authors.affiliation: 1 Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida , St. Petersburg, Florida.
authors.forename: Ellisa Carla
authors.initials: EC
authors.lastname: Parker-Athill
authors.affiliation: 5 Department of Internal Medicine, Center for Comparative Effectiveness Research, University of South Florida Morsani College of Medicine , Tampa, Florida.
authors.forename: Branko
authors.initials: B
authors.lastname: Miladinovic
authors.affiliation: 1 Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida , St. Petersburg, Florida.|2 Department of Psychiatry & Behavioral Sciences, University of South Florida , St. Petersburg, Florida.|3 All Children's Hospital-Johns Hopkins Medicine , St. Petersburg, Florida.|6 Department of Health Policy and Management, University of South Florida , St. Petersburg, Florida.|7 Rogers Memorial Hospital , Tampa, Florida.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Storch
authors.affiliation: 1 Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida , St. Petersburg, Florida.|2 Department of Psychiatry & Behavioral Sciences, University of South Florida , St. Petersburg, Florida.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Lewin
mesh_terms: D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D010865:Pilot Projects
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin
keywords: PANDAS; azithromycin; obsessive–compulsive disorder; pediatric acute-onset neuropsychiatric syndrome; tic disorders