The most appropriate treatment for this patient with medically unexplained symptoms (MUS) is citalopram. This patient has a 3-year history of multiple nonspecific symptoms with an extensive negative evaluation, consistent with the presentation of MUS. Patients with MUS frequently have primary or secondary underlying depression, which may be overlooked during the unsuccessful quest for a unifying or previously undiagnosed organic illness. This patient meets the criteria for depression; he has depressed mood and affect for more than 6 months accompanied by hypersomnia and hopelessness. Antidepressant therapy, such as with the selective serotonin reuptake inhibitor (SSRI) citalopram, is the most appropriate treatment at this time. A systematic review of 94 randomized controlled trials found improvement in symptoms in patients with MUS who were treated with antidepressants.

Although the patient experiences anxiety at night and is unable to sleep well, alprazolam, a benzodiazepine, is a poor choice for chronic management of his anxiety. Alprazolam is associated with sedation, impaired cognition, and a high risk of dependence. This patient's primary symptoms of depression and anxiety will most likely respond to an SSRI.

Lithium would be appropriate if the patient had symptoms consistent with bipolar disorder. This patient has no history of bipolar disorder, and he is not manifesting any symptoms of mania.

Methylphenidate is a central nervous system stimulant that is used in the treatment of attention-deficit/hyperactivity disorder and narcolepsy. It may be used off label for the treatment of depression in adults who are terminally ill or receiving palliative care. First-line treatment of this patient with underlying depression is an SSRI.