The USAF has been was using combinations of the insomnia hypnotics (like Ambien, etc) and amphetamines extensively for awhile in both Iraq and Afghanistan. There's been no small amount of controversy about this; while official policy is that usage is voluntary...well, I think we all know how that would work in practice. There's also been some questioning of its impact in several of the notorious friendly fire incidents. There's been some controversy about that too with several doctors from the services and VA saying there's been official pressure against studies of long-term affects on decision-making.
How to put all this into game terms is a good question. My gut instinct is to let one dosage eliminate all fatigue accumulated over a 48 hour period if followed by an 8-hour period of sleep. I'd consider instituting a general 1-2 point penalty (depending on whether or not you're using d10 or d20) for continued use of more than a week or more.
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