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 PANDAS subgroup.

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:

http://intramural.nimh.nih.gov/research/pdn/web.htm:

Condition	Treatment or Intervention	Phase
Chorea Mental Disorder Diagnosed in Childhood Obsessive Compulsive Disorder Streptococcal Infection Tic Disorder	Drug: Azithromycin	Phase II

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 symptoms 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 the PANDAS 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 and therefore did not decrease the number of neuropsychiatric symptom exacerbations. The failure to provide prophylaxis against GABHS and neuropsychiatric symptom exacerbations was felt to be secondary to poor compliance. We propose to conduct a parallel study of azithromycin and penicillin prophylaxis to determine if the prevention of GABHS infections in the PANDAS subgroup results in a decrease in neurophychiatric exacerbations. To improve compliance, the medication will be administered from blister packs with the day and time designated for each dose. This will allow us to determine the efficacy of antibiotic prophylaxis against GABHS when the antibiotics are taken as directed.

Throat cultures, antibody titers, and symptom ratings will be obtained monthly and used for the determination of a temporal association between the GABHS infections and the neuropsychiatric symptoms. Following a comprehensive baseline evaluation, the participant will be randomly assigned to receive a twelve-month course of either penicillin or azithromycin capsules. We expert that the year long administration of azithromycin or penicillin prophylaxis with adequate compliance will prevent streptococcal infections and result in decreased numbers of neuropsychiatric symptom exacerbations in these children.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
Patients must meet criteria for the PANDAS subgroup, including:
1. A tic disorder and/or obsessive compulsive disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders-IV edition.
2. A history of a sudden onset of symptoms or an episodic course with abrupt symptom exacerbations interspersed with periods of partial or complete remission.
3. Onset of neuropsychiatric symptoms prior to puberty.
4. Evidence of an association between streptococcal infections and the onset of exacerbations of symptoms.
EXCLUSION CRITERIA:
History of rheumatic fever, including rheumatic heart disease and Sydenham's chorea.
History of other central nervous system autoimmune disorders such as Lupus (SLE), multiple sclerosis, Devek disease (optic neuritis), and Behcet disease (oculourethral syndrome).
History of autism.
History of neurologic disorders other than tics and Tourette Syndrome.
History of personal or family allergy to penicillin, erythromycin, clarithromycin, or azithromycin; current treatment with pimozide.

Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  930122; 93-M-0122
Record last reviewed:  April 15, 2004
Last Updated:  April 15, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001359
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-17