HI, thanks for using healthcare magic There is a risk of very serious interaction between zoloft and venlafaxine. It is not recommended for these medications to be used together. Both increase the level of serotonin, a chemical that can be found in the body. Increased levels of serotonin can cause a condition called serotonin syndrome. Serotonin syndrome can cause tremors, seizures, headache, confusion, agitation, increased heart rate, increased blood pressure, increased body temperature. It is possible the combination is contributing to some of his symptoms though it does not usually cause fatigue. It would be best to speak to his doctor about this drug combination. I hope this helps