Having ruled out all other potential causes, one must consider the possibility that true tolerance has developed. When this occurs there are a few strategies that may be helpful. The first step is simply to increase the dose of medication. Patients who have been on stimulants for some time often have a good sense of what sort of dose increase they would need to achieve symptoms control again and their intuitions are generally a good starting point.
Should dose increase fail to bring symptoms under control, one may need to take drug holidays. For instance, one might limit stimulant use to Monday through Friday and take the weekends off. Doing so often provides the patient with a more robust response toward the beginning of the week. The disadvantage of this approach is that a person might find themselves rather lethargic during the weekend. If this is too debilitating, taking 1/2 or even 1/3 dose on the weekends may be enough to re-sensitize the brain without bringing on too much lethargy.
Another approach is to alternate between two stimulants. Because methylphenidate is more chemically distinct from the amphetamine preparations than amphetamine-based stimulants are from each other, switching between a methylphenidate drug and an amphetamine can maintain the benefits of each with less danger of tolerance. For simplicity, alternating every month or two seems to be a reasonable frequency.
Last updated 12/2/17