Table 2 Pharmacological agents selected in the 5-EPIFAT trial

Methylphenidate

Methylphenidate is a psychostimulant which has been frequently studied and is widely prescribed for the medical management of patients with attention deficit hyperactivity disorder [3, 32]. Methylphenidate is considered as one of the promising pharmacological options in improving CRF, which is well tolerated by patients, although the results about its efficacy are mixed [29]. Both NCCN and ASCO recommend psychostimulant drugs (such as methylphenidate) as pharmacological options in active treatment patients, although they note that clinical evidence is limited [33]

Bupropion

Bupropion is a non-serotonergic antidepressant that may be useful in the treatment of CRF. Bupropion is widely available as a generic drug with an excellent safety profile, and there have been frequent requests to investigate bupropion as a pharmacological agent for the treatment of CRF [13]. Bupropion is an antidepressant with a dual effect on the neurotransmitter systems of norepinephrine and dopamine, so psychopharmacologically it shares a wide range of actions with psychostimulants [25]

Ginseng

Thanks to its various pharmacological effects, ginseng is one of the most valuable herbs in herbal medicine. Ginseng is widely used in the United States and other countries, based on the belief that it improves energy levels, and relieves stress and mental and physical fatigue [34]. Panax Ginseng extract has a direct effect on the central nervous system, and the ability to modulate inflammatory cytokines. Despite its frequent use, evidence for its effect on the improvement of CRF is limited [35]. Ginseng is a good treatment option, especially in patients who want to use herbal medicines

Amantadine

Amantadine is a drug approved by the Food and Drug Administration for the prevention of influenza and the symptomatic treatment of Parkinson’s disease, and it is the most widely studied drug for fatigue associated with multiple sclerosis [36]. It is unclear which pharmacological effect may be responsible for the possible anti-fatigue properties of amantadine [37]. According to a Cochrane systematic review study, amantadine appears to be promising in improving fatigue in other chronic conditions, but whether or not it relieves fatigue in cancer patients has not been shown, and should be investigated [15]