Zoloft is an SSRI (selective serotonin reuptake inhibitor). Tramadol is a painkiller with SNRI (serotonin and noadrenalin reuptake inhibitor) properties. This means that both Zoloft and tramadol have an effect on the neurotransmitter serotonin in the brain. This can result in too much serotonin in the brain. This is called Serotonin Syndrom, a very dangerous condition. Never mix multiple drugs that affect serotonin.