The most appropriate next step in the management of this patient who meets the clinical criteria for systemic exertion intolerance disease (SEID), formerly known as chronic fatigue syndrome, is cognitive-behavioral therapy (CBT). She has severe fatigue that has persisted for more than 6 months, is not due to ongoing exertion, is not relieved by rest, and is interfering with pre-illness daily activities. Additionally, the fatigue is accompanied by unrefreshing sleep, difficulty concentrating, myalgia, and arthralgia. The physical examination is normal, and an extensive evaluation for a secondary underlying medical condition, including sleep disorders, was normal. Further diagnostic testing is not indicated, and efforts should now be concentrated on evidence-based management. The two treatment strategies that have been shown to be of greatest benefit in the management of these patients are CBT and graded exercise programs. Improvements in fatigue and physical function have been demonstrated in several randomized controlled trials. CBT, usually performed by trained clinicians, is designed to assist patients in modifying their illness beliefs and supporting behaviors and to incorporate effective coping strategies into daily life.

Approximately 70% of patients with SEID meet criteria for depression, anxiety, or dysthymia. However, this patient does not meet the current DSM-5 criteria for either depression or anxiety. Citalopram, or any other antidepressant, is unlikely to be of major benefit in this patient.

In short-term (4-week) studies, methylphenidate did improve fatigue in 30% of patients with SEID, although long-term effectiveness and potential adverse effects associated with long-term use are unknown. Additionally, in this patient of childbearing age with hypertension, the short- and long-term risks of this medication would be increased. Therefore, methylphenidate would not be the next best step in management.

Although several viruses have been implicated in the development of SEID, no precise cause has been established, and antiviral medications, such as valacyclovir, have not demonstrated any clear benefit.