Hello, Chantix is truly a great medication to help you quit smoking. I’ve had many patients on it and quite a few success stories with that. Likewise Zoloft is equally and effective anti-depressant. I do have concerns that you may be trying to make too many adjustments at once. I am somewhat concerned that going off of the Zoloft, or rather weaning it down, may potentially cause some rebound depression. That poses a little bit of a concern because Chantix does have some psychiatric adverse effects to it, which it does sound like you already know. There is a slight risk of suicidal thoughts with Chantix after it is started. My recommendation to you, and this is what I have told all my patients, as I would make one medication change at a time. If you just started the Chantix then I personally would leave the Zoloft exactly where it is for right now. Focus on trying to quit smoking using the Chantix first, and then down the road a little you can start working on weaning off of the Zoloft. That would be my recommendation, if you start to have any negative symptoms wow you’re going up on the Chantix and down on the Zoloft you likely will not know which one of the medication changes is causing your symptoms. Take care. Hope I have answered your question. Let me know if I can assist you further. Regards, Dr. David Girardi, Internal Medicine Specialist