Everything in the right 'high dosage' could be deadly. The more (different) substances you combine the more your body screws up, maybe you puke earlier than from a single substance OD? I'd prefer combining opiates with benzos to achieve respiratory depression and death since that sounds less painful than a body metabolizing uppers and downers at the same time. Can't find the right English words atm to describe what happens in your body but it's easy to google up