A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections

Biol Psychiatry. 1999 Jun 15;45(12):1564-71. doi: 10.1016/s0006-3223(99)00020-7.


Background: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham's chorea. Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and streptococcal-triggered symptom exacerbations.

Methods: Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study. Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V. Tic, OCD, and other psychiatric symptoms were monitored monthly. Throat cultures and streptococcal antibody titers were also obtained.

Results: There were an equal number of infections in both the active and placebo phases of the study. There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases.

Conclusions: Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / therapeutic use*
  • Anxiety Disorders / microbiology*
  • Anxiety Disorders / prevention & control*
  • Child
  • Child, Preschool
  • Cross-Over Studies
  • Depressive Disorder / microbiology*
  • Depressive Disorder / prevention & control*
  • Double-Blind Method
  • Female
  • Humans
  • Lactams
  • Male
  • Obsessive-Compulsive Disorder / diagnosis
  • Obsessive-Compulsive Disorder / psychology
  • Penicillins / therapeutic use*
  • Pilot Projects
  • Rheumatic Fever / prevention & control
  • Secondary Prevention
  • Streptococcal Infections / complications*
  • Tic Disorders / diagnosis
  • Tic Disorders / psychology


  • Anti-Bacterial Agents
  • Lactams
  • Penicillins