Thanks for reply Dave. I had a great run with a low dose of Paxil CR over the past 18 years. I never considered going off of it. Now, following a surgery, I have debilitating anxiety heaped upon now worsening depression. Still taking the Paxil, but the Dr. is now attempting to get me on other SNRI and SSRI medications which has proved problematic. I totally agree there is a significant genetic component. And based on The Genesight test there are a bunch of headwinds including the genetics that can limit the effectiveness of the medications in general as well as a very short list of well metabolized medications. My Doctor is really struggling with being able to provide any proper guidance now. He recommended Ketamine therapy but was declined due to cardiac issues. Now, he is thinking anticonvulsants to assist with the anxiety. My wife would like me to get off all the medications, but she also has no idea of the intensity of both emotional and physical pain is involved with daily life. Not sure what to do next. None of the options seem really solid at this point.