A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) and/or tic
disorders has been identified who share a common clinical course characterized by dramatic
onset and symptom exacerbations following group A beta-hemolytic streptococcal (GABHS)
infections. This subgroup is designated by the acronym PANDAS (Pediatric Autoimmune
Neuropsychiatric Disorders Associated with Streptococcal infections). There are five
clinical characteristics that define the PANDAS subgroup: presence of OCD and/or tic
disorder; prepubertal symptom onset; sudden onset or abrupt exacerbations
(relapsing-remitting course); association with neurological abnormalities (presence of
adventitious movements or motoric hyperactivity during exacerbations); and temporal
association between symptom exacerbations and GABHS infections. In this subgroup, periodic
exacerbations appear to be triggered by GABHS infections in a manner similar to that of
Sydenham's chorea, the neurological variant of rheumatic fever.
Rheumatic fever is a disorder with a presumed post-streptococcal autoimmune etiology. The
streptococcal pathogenesis of rheumatic fever is supported by studies that have demonstrated
the effectiveness of penicillin prophylaxis in preventing recurrences of this illness. A
trial of penicillin prophylaxis in the PANDAS subgroup demonstrated that penicillin was not
superior to placebo as prophylaxis against GABHS infections in these children, but this
outcome was felt to be secondary to non-compliance with treatment, and there was no decrease
in the number of neuropsychiatric symptom exacerbations in this group. In a study comparing
azithromycin and penicillin, both drugs were completely effective in preventing
streptococcal infections - there were no documented titer elevations during the year-long
study period for children taking either penicillin or azithromycin. Comparable reductions
in the severity of tics and obsessive-compulsive symptoms were also observed. Thus,
penicillin was not performing as an "active placebo" as originally postulated, but rather
provided effective prophylaxis against Group A beta-hemolytic streptococcal. Both
azithromycin and penicillin appear to be effective in eliminating GABHS infections, and
reducing neuropsychiatric symptom severity; thus, between-group differences are negligible.
Since increasing the "n" to demonstrate superiority of one prophylactic agent over another
would be impractical, we have amended the study design to address two issues:
1. To determine if antibiotics prophylaxis against GABHS infections is superior to placebo
in prolonging periods of remission among children in the PANDAS subgroup.
2. To determine if antibiotics prophylaxis against GABHS infections is superior to placebo
in improving overall symptom severity for obsessive-compulsive symptoms and tics among
children in the PANDAS subgroup.
Because penicillin has a narrower therapeutic index and is less expensive than azithromycin,
it is the preferable prophylactic agent. Further, penicillin (250 mg orally twice a day)
has a long history of providing safe and effective prophylaxis for rheumatic fever and is
the first line oral therapy recommended by the American Heart Association. Thus, penicillin
has been chosen as the prophylactic antibiotic in the present study. Blister packs are used
to increase compliance and to allow for easier documentation of missed doses.
The purpose of this study is to determine whether penicillin prevents the symptoms of
Obsessive-compulsive Disorder (OCD) and tic disorders from recurring in children with
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS).
A subgroup of children with childhood-onset OCD and/or tic disorders share a common clinical
course characterized by dramatic onset and symptom exacerbations following scarlet fever or
strep. throat infections. Such infections may be prevented by the prophylactic (preventative
dose) administration of antibiotics, such as penicillin. This study will determine the
effectiveness of penicillin prophylaxis in preventing relapses of OCD and/or tics in the
Participants receive a comprehensive psychiatric, neurological and physical evaluation.
Children will initially receive penicillin tablets, and then will be randomly assigned to
receive either penicillin or placebo tablets for 6 months. Children will be monitored
monthly by either in-person visits or a telephone interview. Any child who has a significant
increase in his or her OCD or tics is taken off the randomized medication and put on
open-label penicillin for the rest of the study.
For more information about this study please visit the Official P.A.N.D.A.S. Web Page at the
following web address:
1. Ages 4 - 18 years
2. Fulfill criteria for membership in the PANDAS subgroup:
1. Presence of OCD and/or tic disorder
2. Prepubertal symptom onset
3. Abrupt onset and episodic (relapsing-remitting) symptom course
4. Association between symptom exacerbations and GABHS infections
5. Presence of choreiform movements or other neurological abnormalities during
Because "time to relapse" is one of the primary outcome variables, children will not be
eligible for randomization until their symptoms are in (at least partial) remission. At
the time of randomization, symptom severity scores should be less than 50% of the child's
previous maximum score on both the CY-BOCS and YGTSS, and no higher than a total score of
20 on the CY-BOCS or 30 on the YGTSS.
1. Personal history of penicillin allergy
2. History of rheumatic fever, including Sydenham's chorea
3. Diagnosis of autism, schizophrenia or other psychotic disorder
4. Chronic illnesses, particularly neurologic and immunologic disorders