Kiki Chang, MD, is a child, adolescent and adult psychiatrist in private practice in Palo Alto, CA. From 1999 – 2017 he was on the faculty of the Stanford University School of Medicine, Division of Child Psychiatry, where he was Director of the Pediatric Bipolar Disorders Clinic and Research Program, specializing in pediatric psychopharmacology and treatment of depression and bipolar disorder in children and adolescents. His research includes brain imaging, genetics, and medication and psychotherapy trials, designed to identify those at highest risk for bipolar disorder and methods to intervene to prevent its onset.
In 2012, Dr. Chang co-founded the Stanford Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) Clinic and Research Program at the Lucille Packard Children’s Hospital at Stanford. He then expanded his research to include immunologic, inflammatory, and brain imaging research in PANS in order to understand the medical etiology and better treatment algorithms for these afflicted youth.
Dr. Chang graduated cum laude from Princeton University in 1988 and received his M.D. from the Tufts University School of Medicine in 1993. He completed his general psychiatry residency at the University of Cincinnati and his child psychiatry fellowship at Stanford University. After a postdoctoral research fellowship, Dr. Chang joined the Stanford faculty in 1999.
Dr. Chang is the recipient of the 2003 American Psychiatric Association/AstraZeneca Young Minds in Psychiatry Award. His research has been funded by the NIMH, NARSAD, the Prechter Fund, the Hahn Family, and other private donors. He is the recipient of multiple K-Awards and R01 grants from the NIMH.
Dr. Chang is the author of over 130 papers and book chapters regarding bipolar disorder and PANS and has presented widely at national and international scientific conferences and meetings.
Neuropsychiatric Disorders in Children: An Interview with Co-Founder of the Stanford PANS Clinic, Dr. Kiki Chang
Thank you to Dr. Chang for allowing the executive director and founder of Neuroimmune Foundation, Anna Conkey, to interview him.
How did you first learn of PANS/PANDAS and what motivated you to begin treating children with PANS/PANDAS?
I first became interested when I realized that some patients who were referred to me for consultation with presumed bipolar disorder had an unusual onset and/or course. These patients were also treatment resistant to standard treatments for bipolar disorder. I discovered that many of them either met PANS criteria or had a periodic mood disorder that included elements of catatonia, or unusual mental status changes. It made sense that underlying immunologic factors were at least partially responsible. These patients responded to immunomodulatory treatments rather than typical psychotropics.
I also started collaborating with a pediatric rheumatologist, Dr Jennifer Frankovich, who was interested in the same patients from the other end – many of her patients with rheumatologic disorders also had psychiatric symptoms including OCD. When we realized our shared interests and that these patients fell under the PANS rubric, we decided to join forces with Margo Thienemann and start the PANS Clinic at Stanford.
Do you ever treat children who did not have an abrupt or acute onset, and if so, do they respond similarly to children who did have an abrupt onset?
Yes I do, and not always. Abrupt is an arbitrary but necessary concept – is it 48 hours? 72 hours? In our 2013 Expert Consensus Diagnostic meeting we agreed on 72 hours but many kids with sub-acute onset, say one week, will still likely have the same underlying issues – it’s just that if you keep stretching out that onset time, then it becomes a gray area and muddies the research waters. The longer and more gradual the onset, the less likely it will fit clear PANS criteria and also have the same treatment response.
How do you determine which patients with PANS would benefits from psychiatric medications and when to introduce them?
I think our guidelines present this issue fairly well (first author Dr Margo Thienemann, JCAP 2017). If needed, psychiatric support is always indicated – to help alleviate severe anxiety, agitation, sleeplessness, etc. If patients are functioning OK without them, then I prefer to treat medically as long as possible before using psychotropics. At some point, whether due to only partial treatment response medically, or other factors, psychotropics make a lot of sense.
Is there a particular class of psychotropic medication that tends to be more effective in children with PANS?
I have a particular fondness for lithium, in that for youth with severe mood disruption, including a bipolar like picture, even in a PANS context, it can be very useful. Yes, lithium has potential side effects, but if it works, it works great. I could go on and on about the benefits of lithium and how it is missing in our soil, water, and diets, but you probably have a word limit.
Are there any anomalies you see when treating children with PANS with psychotropic medications?
Not sure what you mean – do you mean do SSRI’s sometimes worsen their course? Sure, but not always. Also antipsychotics sometimes cause EPS symptoms more so than would be expected. Probably due to the dopamine dysregulation going on in the basal ganglia being compounded by a dopamine receptor antagonist.
Many medical clinicians have interpreted the JCAP treatment guidelines as step one, “Psychiatric and Behavioral Interventions,” step two, “Use of Immunomodulatory Therapies,” and step three, “Treatment and Prevention of Infections.” As one of the authors, was the intent to suggest psychiatric and behavioral interventions prior to other interventions or has this been misinterpreted?
Yes, that would be a misinterpretation of the treatment guideline! It’s really based on the patient’s presenting issues. All three approaches should be considered initially. Theorder depends on what’s going on with the individual patient. If there is clear infection, then of course treat it first. If psychiatric symptoms are severe and need urgent stabilization, then do that. I had no idea people were interpreting the guidelines that way, I think the introduction paper to the guidelines explains the overall approach well.
Have you treated any patients with longstanding diagnoses of bipolar, schizophrenia, depression, or any mood disorders whose symptoms resolved with immunomodulatory therapies?
Yes, on occasion. I saw the recent report from Japan about the patient with schizophrenia whose symptoms resolved with bone marrow transplantation after a subsequently diagnosed cancer. Absolutely make sense in SOME cases. Great example – clozapine has a long history of working where other antispychotics have failed – for schizophrenia or bipolar disorder. Why? The receptor profile is similar to other atypical antipsychotics – so what sets it apart? Well, the one main side effect people have to check for is agranulocytosis, or basically suppressing the body’s production of white blood cells. Hmm…so a potential “side effect” is suppressing the immune system? Seems like not a coincidence to me – it probably affects the immune system in some way even when not having full suppression of neutrophil production…and that is in my opinion probably why it works when other medications don’t…that perhaps those patients have a more immune-mediated illness.
What is your approach to managing children with autism who develop neuropsychiatric symptoms? How does this differ from your approach to those without autism?
Tough question. Certainly just because you are diagnosed with an autism spectrum disorder doesn’t mean you CAN’T develop a PANS condition. Some might argue that these kids might be actually MORE susceptible to such a condition, given the propensity of kids with ASD to have OC symptoms and/or tics. My approach does not differ really for treatment, but for diagnosis there must be a clear acute onset meeting PANS criteria in order to say, yes this is PANS and let’s treat accordingly.
If you could snap your fingers and have any research on PANS completed tomorrow, what would you most like to see studied?
Egads, great question, there are so many studies I would like to see done. I’d have to say probably first to have placebo controlled steroid trials in youth with PANS. Clearly clinically steroids can be effective, but it would help tremendously to have this proven in a RDBCT. Oh and having a cleaner and longer IVIG trial completed – and if positive then getting an indication so that insurance companies will all have to cover it for these kids.