The use of amphetamines or other stimulants as adjuvant medications can be tempting when treating chronic pain patients, especially high-dose therapy patients in whom side effects such as sedation can become more prevalent. In terminal cancer patients, the use of amphetamines as adjuncts is even more pressing because of the emphasis on side effect reduction and improvement in the patient's quality of life in their remaining months.
Although one would think that there would be many studies looking at amphetamines to mitigate opioid-induced sedation, in fact there are only a few randomized, double-blinded, placebo-controlled, clinical trials (Wilwerding et al. 1995). In one such study conducted in patients with terminal cancer (Bruera et al. 1986), patients were given mazindol or placebo for 1 week and then switched to the other treatment/placebo arm. During the study period there were no differences in patient sedation as primarily measured by the number of hours slept, but the mazindol-treated group had much higher prevalence of side effects such as anxiety, nausea, and sweating.
Another similar study (Bruera et al. 1992) included terminal cancer patients on continuous intravenous opioid infusions. The patients were double-blinded and randomized to a 3-day treatment course of methylphenidate versus placebo. The patients were then evaluated every 6 h for markers of sedation including drowsiness, confusion, and cognitive function. After 3 days of treatment, reports for all three endpoints were improved with drowsiness (8 versus 35%), confusion (8 versus 22%), and cognitive function (25 versus 1%) in the methylphenidate versus placebo groups, respectively.
There are obvious limitations that preclude applying these outcomes in favor of chronic amphetamine use to counteract opioid sedation (Max and Gilron 2001). In prescribing amphetamines, one has to remember that these are controlled drugs with a high potential for abuse and diversion (Hertz and Knight 2006). Chronic amphetamine use runs its own risk with cardiopulmonary and central nervous system effects as well as the development of tolerance. Hence, alternate drug strategies to mitigate sedation such as evaluation and treatment for other causes of sedation such as anemia, endocrinopathies, or depression should be undertaken. Simple medication changes such as changing to sustained release opioid medication may also help as these formulations are less associated with sedation.
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