Bacteria carry substances on their surface called antigens. When antigens come into contact
with the right kinds of cells in the body an immune reaction is caused. This reaction is
often the symptoms of sickness that a patient feels.
In order for the body to fight off the attack of antigens, it creates substances called
antibodies. Antibodies counter the action of antigens and make the bacteria harmless.
However, the immune system must learn how to make the right antibodies for the right
antigens. Sometimes the body creates antibodies that confuse normal tissues as foreign and
attack them. This is called an autoimmune reaction and sometimes occurs when the body is
exposed to certain bacteria.
One bacteria known for causing autoimmune reactions is Group A beta-hemolytic Streptococcus
(GABHS). This bacteria often causes throat infections commonly known as "strep throat".
Some researchers believe that the autoimmune reaction associated with strep throat
infections may cause neuropsychiatric disorders, like obsessive-compulsive disorder and/or
tic disorder in children. As a result, each time a child with one of these disorders
experiences an infection with GABHS his/her symptoms can reoccur or worsen. Researchers
believe that by giving patients a certain antibiotic, they can prevent GABHS infection and
thus prevent the return of symptoms.
This study is designed to test the effectiveness of the antibiotic Amoxicillin for the
treatment of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal
infections (PANDAS). Patients will receive Amoxicillin for six weeks and placebos "inactive
sugar pills" for six weeks in order to see if the medication is truly working.
Effectiveness of the treatment will be based on the presence or absence of symptoms. If at
the end of the study Amoxicillin is proven to be effective treatment for PANDAS patients may
be offered the opportunity to continue taking the medication for an additional six months.
An increasing body of evidence suggests that Group A beta-Hemolytic Streptococcal throat
infections (GABHS) may trigger the onset of obsessive-compulsive disorder (OCD) and/or tic
disorder in certain vulnerable children via an autoimmune process. In this subgroup of
children with childhood-onset OCD and tic disorders, preliminary data suggest some children
have a rapid response to amoxicillin. After only 24 to 48 hours of treatment, they have a
dramatic reduction in OC symptoms and tics. To date, we have observed this phenomenon in at
least 5 children, each of whom relapsed when the amoxicillin was stopped. These
observations raise a number of questions, including whether or not amoxicillin has a direct
central nervous system (CNS) effect or an indirect effect through perturbations of the
immune system (e.g., cytokine shifts).
The purpose of this study is to determine if amoxicillin is an effective treatment for
PANDAS, as well as examining possible mechanisms of this effect. We propose to do this with
a 3-month double-blind placebo-controlled crossover trial of amoxicillin treatment with a
randomized A-B-A-B design. Outcome measures will be blinded ratings of tic severity,
standardized measures of psychopathology, and immunologic assays (such as type I and type II
Subjects with presence of OCD and/or tic disorder: Must meet lifetime diagnostic criteria
(DSM III or DSM IV) for obsessive compulsive disorder or a tic disorder.
Pediatric onset: Symptoms of the disorder first become evident between 3 years of age and
the beginning of puberty, as is generally true for rheumatic fever.
Episodic course of symptom severity: Clinical course is characterized by the abrupt onset
of symptoms or by dramatic symptom exacerbations. Episodic course is characterized by
waxing and waning or symptom severity with greater than +20 percent fluctuation from
Association with GABHS infection: Symptom onset or exacerbations must be temporally
related to group A B-Hemolytic Streptococcal infections (GABHS), i.e., associated with
positive throat culture and/or elevated anti-GABHS antibody titers.
Association with neurological abnormalities: During symptom exacerbations, patients will
have an abnormal neurological examination, such as motoric hyperactivity and adventitious
movements (i.e., choreiform movements or tics).
Subjects must report history of improvement in their tics and/or OCD when treated with
No subjects who meet criteria for Autism.
No subjects who have neurologic disorders other than tics/TS.
No subjects who have and IQ less than 80.
No subjects who have a serious concurrent or chronic medical illness.
No subjects who have a history of penicillin or amoxicillin allergy.
No subjects with history of noncompliance with medical procedures.