Advances in medicine come in all shapes and sizes: vaccines, antibiotics, anti-virals, immune system boosters and reducers, technological changes and recently, the hope that faster, cheaper and more accurate genetic analysis can bring us the new approach to medicine and medications: personalized medicine.

As I have mentioned in a previous blog, a leading proponent of personalized medicine has been Dr Eric Topol, editor-in-chief of Medscape and director the Scripps Translational Science Institute.  Translational science is an important concept.  It means taking the bench sciences and research and translating them into actionable information for people who actually care for patients.  Dr Topol, himself a cardiologist, has written a great book on the subject called The Creative Destruction of Medicine.  Check it out.

At Kartini Clinic we are always searching for better ways to deal with medication for our patients.  We have often found it helpful to use the antipsychotic drug Olanzapine, in small doses, for the delusional fear of food and fat in anorexia nervosa.  It is the mainstay of our success with young patients with food phobia.  But we can’t use it in every patient, nor would we want to, and when we do use it we want to use it for the shortest period of time that we can.  For some patients Olanzapine is a game changer; for others it helps a little, and some seem to show little to no effect.  

And, of course, like all clinics which treat many patients with complex brain disorders, such as an eating disorder AND depression or an eating disorder AND obsessive compulsive disorder or an eating disorder AND anxiety, we have experience using the class of drugs called SSRI’s (Prozac, Paxil, Celexa, Lexapro, etc).  Once again, some patients respond brilliantly, some respond a little, and some seem to get no help at all.  Frustrating.

So in thinking about medication and kids with eating disorders, we have piloted a few programmatic approaches to deal with safety and efficacy which, as far as we can tell, appear to be unique to Kartini Clinic.  As Dr Moshtael and I are both pediatricians, we tend to be conservative with medication.  Adult doctors seem to throw one medication after another at adults and see what sticks. “Just try it”, is often the motto.  We hate this approach and refuse to use it with our children, who, after all, have young, growing brains and are precious beyond telling to their parents.  So our general philosophy has been: “keep the formulary small and try to use one or at most two medications at a time”, “use no sleeping pills”, and “use no addictive drugs such as benzodiazepines to treat anxiety”.  We also say: “use the smallest dose that’s effective and for the shortest period of time you can.”  

Well, that’s all very well and good, but it’s not advanced science, it’s just a conservative approach to safety.

A few years ago, when thinking about my own experience with tuberculosis and leprosy as a young doctor in the South Pacific, and gnashing my teeth over the fact that our young patients were often “non-compliant” with their medication, I hit on a game changing approach for us: “directly observed therapy”, such as is practiced for multiple drug-resistant TB.  Directly observed therapy means that a parent, in the case of our patients, (a community health nurse in the case of resistant TB in the Pacific islands and elsewhere) is placed in charge of all medication and gives it directly to the child every day “babybird style” directly into their mouth, followed by two sips of water and swishing the mouth.  Such directly observed administration follows our model of having parents in charge of food in family-centered treatment.  

Suddenly, safety and efficacy improved for our patients immensely.  Why don’t all doctors who treat children do it this way?  Well, for one, they don’t have the family-centered treatment approach that places parents in charge.  In the past, as a general pediatrician, I have seen adults abdicate control of insulin to their diabetic six year olds. Don’t get me started!  These are dangerous and important drugs, folks, be they insulin, metformin, Olanzapine, Prozac or anything else, and we must insure safety, at least for children.  These medications are too important to take for three days and forget on the fourth.

So DOT BB S&Sx2  our shorthand for “directly observed therapy, baby-bird style, swish and swallow twice” has gone a long way towards ensuring stability and accuracy of dosing as well as reducing non-accidental overdose in teenagers, but it is still the shallow end of the pool.

What is the deep end of the pool in personalized medicine?  Genetic testing.  And we have just begun to use it.

A new firm called Genomind reached out to us about non-invasive (cheek swab or saliva) genetic tests which focus on testing for individual response to psychoactive medication.  To be certain that this was what it purported to be, I had myself tested first.  That way I could feel free to discuss the results, if any, with our families and my readers.

The results?  I discovered that I carry a variant of the gene SLC6A4 which codes for “slow response, poor response and/or likelihood of adverse events with SSRI’s”.  Good to know!

They further elaborate on my genetics, saying: “The serotonin transporter protein is a presynaptic transmembrane protein responsible for serotonin reuptake. The patient (me)  exhibits a variant of the serotonin transporter gene which the literature suggests may result in reduced reuptake of serotonin, less satisfactory response to SSRI-based treatments, and potentially a greater risk of adverse effects, compared to patients without this variant.” Citations are included for all of these assertions.   

They go on to say: “This variant has been associated in published literature with lower stress resilience and higher rates of PTSD”.  Well, I don’t know about lower stress resilience, as I have had a fair amount of stress to deal with in my life and have seemed fairly resilient, but it is true that my own father, obviously one of my closest genetic relatives, suffered from PTSD from severe combat experiences during WWII.

Further, the study states, I have a variant of the 5HT2C gene which means I would be at high risk for the side effect of weight gain were I ever to use Olanzapine. (Glad not everyone carries this gene variant!)  I also have a deletion in the DRDR2 gene which means that Olanzapine would not only affect my weight metabolism, but it also likely would not work. Again, good to know.

I fortunately have the normal MTHFR (no jokes, please) gene variant which means I would respond to drugs affecting the methylenetetrahydrofolate reductase system, such as Deplin, which we occasionally use in depression.  I have normal CY2D6 genes as well. Were this not the case I would likely metabolize psychotropic medications too rapidly and/or unpredictably, altering their response to them.

We have been very excited about the possibilities of adding this personalized genetic information to our prescribing armamentarium.  It would be great to know in advance which drugs should or should not be expected to work in an individual patient.  This may turn out to be the ultimate weapon in increasing safety and efficacy and go a long way towards making sense out of who responds to medication for depression, anxiety and other brain disorders and who does not. We have just begun to test those patients whose parents wish it and whose insurance will cover it.

Our patients and their parents are excited about the possibilities.  We are excited.  Targeted genetic testing is no doubt the future of personalized medicine.  And we, at Kartini Clinic, intend to embrace it.