Conference Coverage

Latest PANS trials suggest cause may be treatable


 

REPORTING FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE

– New controlled trials in the treatment of pediatric acute neuropsychiatric syndrome (PANS) support the hypothesis that the cause may, in fact, be treatable, an expert said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

PANS and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are controversial diagnoses. But ongoing research has expanded the body of literature describing symptoms and evaluating treatments, according to an overview from Barbara J. Coffey, MD, division chief in child and adolescent psychiatry at the University of Miami.

PANS and PANDAS, which are clinical diagnoses of exclusion, are characterized by an abrupt onset of one or more neuropsychiatric symptoms in children that can include signs of obsessive-compulsive disorder (OCD), tics, anxiety, irritability, and behavioral changes. Despite more than 15 years of clinical and experimental studies, almost all aspects of PANS and PANDAS remain controversial, Dr. Coffey said.

“Many pediatricians I work with do not want to see these kids, because they really do not know what to do,” she reported.

A young boy presses his temples SIphotography/Thinkstock
PANDAS is a subset of PANS. The difference is that PANDAS is defined by the presence of a suspected trigger, particularly evidence of a recent strep infection. PANS is not defined by a precipitating factor, although many, including the organizers of the PANDAS Network (www.pandasnetwork.org), consider both conditions to be the result of a trigger-driven autoimmune inflammation of the central nervous system.

This prevailing conception has led to treatment trials with antibiotics for the underlying infection and, most recently, with intravenous immunoglobulins (IVIG) to prevent cross-reactive antibodies induced by infection. Dr. Coffey, reviewing several recently published studies, noted that there have been signals of activity suggesting “there may be something there.” However, she cautioned that the data are inconclusive.

Of recent studies, a trial with azithromycin in children with PANS generated somewhat positive findings (J Child Adolesc Psychopharmacol. 2017;27[7]:640-51). In this study, 31 children aged 4-14 years were randomized to receive azithromycin or placebo for 4 weeks. They were evaluated via the Children’s Yale–Brown Obsessive Compulsive Scale (CY-BOCS) and the OCD Clinical Global Impression Severity (CGI-S OCD) scale.

The study associated azithromycin with a significant reduction in symptoms as measured with CGI-S OCD (41.2% vs. 7.1%; P = .045), but no difference was found in response as measured with the CY-BOCS, which Dr. Coffey described as the more conservative measure. Even when measured with the CGI-S OCD scale, symptom improvements were modest. But the authors concluded that azithromycin “may be helpful” for the control of neuropsychiatric symptoms.

In a trial with IVIG, 35 children with PANDAS were randomized to IVIG or placebo (J Am Acad Child Adolesc Psychiatry. 2016;55[10]:860-7). The primary outcome was at least a 30% reduction in CY-BOCS at 12 weeks. Nonresponders at 12 weeks were permitted 12 more weeks of treatment with open-label IVIG.

Twice as many patients receiving IVIG, compared with those on placebo, reached the primary outcome (24% vs. 12%), but the study was small and the difference did not reach significance. However, the authors reported that the mean CY-BOCS improvement from baseline on IVIG, which was well tolerated, was 55% at week 12 and 62% at week 24. The authors suggested that larger trials are warranted.

“One critique of this study is that all of the patients were placed on prophylactic antibiotics, which may have attenuated the response,” Dr. Coffey said. In outlining these results, she emphasized: “This is not something I am recommending. I just want to acquaint you with what is going on out there.”

None of the most recent trials provide conclusive support for therapy targeted at infection or an autoimmune process in PANS or PANDAS, but Dr. Coffey indicated that there are data to support the hypothesis that infection can be a trigger of neuropsychiatric pathology. One of the most recent sets of data come from a recently published Scandinavian cohort study with 17 years of follow-up (JAMA Psychiatry. 2017;74[7]:740-6). That study associated pediatric infections of any kind, not just streptococcal infections, with an elevated risk of mental disorders – particularly OCD and tics.

Overall, the evidence base is growing to suggest “antibiotics and immune therapy may be beneficial, but the jury is not in yet for which patients, how much, and how long,” Dr. Coffey said. She is aware of clinicians who are now using antibiotics empirically to control neuropsychiatric symptoms in PANDAS but cautioned that more investigation is needed.

Dr. Coffey reports financial relationships with Genco Sciences, Neurocrine Biosciences, Shire, and Teva/Nuvelution.

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