In cancer patients, diagnosis and treatment of depression require a high index of suspicion and regular, careful follow-up. Ideally, only patients with clinically significant or progressive symptoms are offered antidepressant therapy. When the diagnosis of depression is in doubt, however, it may be best to seek psychiatric consultation.

Antidepressants
Selected antidepressants used in cancer patients are listed in Table 1. No antidepressant has been shown to be more effective than any other in the cancer setting. Often, the choice of an antidepressant is based on side-effect profile.

In the general population, antidepressants often take at least 2 weeks or longer to produce initial relief of symptoms. As a general rule, antidepressant therapy should continue for 4 to 6 months after symptoms stabilize.

Selective serotonin reuptake inhibitors (SSRIs), such as citalopram(Drug information on citalopram) (Celexa), escitalopram(Drug information on escitalopram) (Lexapro), fluoxetine(Drug information on fluoxetine) (Prozac, Sarafem), paroxetine(Drug information on paroxetine), and sertraline(Drug information on sertraline) (Zoloft), are often used in patients with cancer because of their benign side-effect profile. In particular, their lack of anticholinergic and α-adrenergic–blocking properties makes them attractive options for patients with a serious medical illness. SSRIs are rarely lethal in overdose, making them a reasonably safe choice in the treatment of patients experiencing suicidal ideations.

Side effects Common side effects of SSRIs include mild nausea, which tends to improve with continued use; reduced appetite; sexual dysfunction, including decreased libido, impotence, and anorgasmia; jitteriness; and insomnia. Paroxetine, in particular, may cause sedation; other side effects include dry mouth, rash, and weight gain.

Dosage In ambulatory patients with normal metabolic function, SSRIs can be started at the same doses used in general psychiatry (10 mg once daily for escitalopram; 20 mg once daily for citalopram, fluoxetine, and paroxetine; 50 mg once daily for sertraline). These doses can be increased if there is no response within 2 to 3 weeks.

Hospitalized or elderly patients, those with compromised renal or hepatic function, and those receiving highly emetogenic treatments should be started at one-half or even one-quarter of these starting doses, which can then be increased if tolerated.

Atypical and newer antidepressants Bupropion (Wellbutrin) is a well-tolerated medication that works to increase norepinephrine(Drug information on norepinephrine) levels in the brain. In addition to its antidepressant effects, bupropion is activating and may help to improve attention. Unlike SSRIs, it is rarely associated with sexual dysfunction. A note of caution, however, is that bupropian lowers the seizure threshold and should not be used in patients with a history of seizures.

Venlafaxine (Effexor), mirtazapine(Drug information on mirtazapine) (Remeron), and duloxetine(Drug information on duloxetine) (Cymbalta) are newer agents with selective effects on serotonin and norepinephrine metabolism. They should be started at low doses in order to establish tolerability. Venlafaxine may be quite effective against treatment-induced hot flashes. It tends to have an intense discontinuation syndrome, and patients should be titrated off slowly. Mirtazapine has sedative, appetite-stimulating, and antiemetic effects, which can all be useful in selected cases. Duloxetine is approved for treatment of diabetic neuropathy and may have applications in the depressed cancer patient with neuropathic pain.

Psychostimulants
Psychostimulants that have direct or indirect dopamine(Drug information on dopamine)-agonistic properties, such as methylphenidate(Drug information on methylphenidate), have an established role in the treatment of depression in the medically ill. Psychostimulants are activating agents useful in patients with psychomotor retardation, deconditioning, or apathy states associated with depression, as well as in those with CNS disease or treatment side effects.

The antidepressant effects of psychostimulants may be seen more quickly than those of first-line antidepressants. Improvements in mood, physical activity, well-being, and appetite are sometimes observed within 24 to 48 hours of the initiation of psychostimulant treatment.

Side effects Like other activating agents, psychostimulants may cause insomnia, decreased appetite, GI upset, anxiety, palpitations, and even arrhythmia. Pulses should be monitored with their use.

Dosage Initial dosing should be conservative (ie, 2.5–5 mg/d, the latter in divided doses) for methylphenidate. If tolerated, stimulant doses can be increased until a therapeutic effect is achieved or side effects develop. To prevent insomnia, afternoon doses should not be administered after 2 pm.