Benzodiazepines can be used to effectively treat the anxiety that may be associated with depression. In patients receiving antidepressant medications and benzodiazepines concomitantly, the latter drugs may be discontinued after patients' depressive symptoms begin to abate; however, both agents can be continued safely if needed. Benzodiazepines should never be stopped abruptly because withdrawal symptoms with possible seizures may occur. The dose of benzodiazepines should be tapered slowly at a rate of approximately 25% every 3 to 4 days.
Clinical experience (see Table 3) suggests that analeptic agents (e.g., methylphenidate and dextroamphetamine) are useful at low doses for patients whose symptoms include depressed mood, apathy, decreased energy, poor concentration, and weakness.[Level of evidence: II] They are particularly useful for patients with advanced cancer who have a limited life expectancy (weeks to a few months). Compared with traditional antidepressants such as the TCAs and SSRIs that take 3 to 4 weeks to take effect, the psychostimulants often demonstrate antidepressant effects within a few days of starting treatment. They promote a sense of well-being, decreased fatigue, and increased appetite. Analeptic agents can be helpful in countering the sedating effects of opioids, and in comparison with antidepressants, they are rapidly effective. Adverse effects associated with analeptic agents include insomnia, euphoria, and mood lability. High doses and long-term use may produce anorexia, nightmares, insomnia, euphoria, or paranoia.
Methylphenidate and dextroamphetamine are administered in divided doses early in a patient's waking cycle to avoid sleep disturbances (e.g., insomnia and nighttime arousal). Like benzodiazepines, these medications are adjuncts to antidepressant medications; they may be started concomitant with an antidepressant and discontinued when depressive symptoms abate.[37,38]
Table 3. Clinical Trials of Psychostimulants in Cancer Patients
|Meyers et al. 1998 
||Brain tumor; N = 30
||? mood, ? cognition, ? function
|Olin and Masand 1996 
||Mixed cancer; N = 59; chart review
||dextroamphetamine (Dexedrine); methylphenidate (Ritalin)
||? depression, ? appetite
|Bruera et al. 1992 
||Cancer pain vs. opioid infusion; N = 20
||methylphenidate (Ritalin); placebo
||? cognition, ? sedation
|Fernandez et al. 1987 
||Mixed cancer; rapid onset; N = 30
||methylphenidate (Ritalin; up to 80 mg)
|Bruera et al. 1986 
||Pain; double-blind cross-over study; N = 24
||? pain, ? appetite, no effect on mood
|Joshi et al. 1982 
Monoamine oxidase inhibitors
The use of monoamine oxidase inhibitors (MAOIs) in the cancer population has been limited because the nutritional requirements of a tyramine-free diet are generally more difficult to accomplish in patients receiving antineoplastic treatments. MAOIs are contraindicated in patients receiving opioids, sympathomimetics, and procarbazine because of the potential for developing hypertensive crisis.
MAOIs may cause adverse reactions when taken with other medications and certain foods. MAOIs impair the metabolism of morphine and other opioids as well as barbiturates and may lead to exaggerated ventilatory depression. Meperidine HCl (Demerol), an opioid, has been associated with hypertension, hyperpyrexia, skeletal muscle rigidity, seizures, and coma when used with MAOIs. Exaggerated effects of antihistamines, anticholinergics, and tricyclic antidepressants may be secondary to impaired metabolism by MAOIs. In addition, the hypoglycemic effects of insulin and oral sulfonylureas may be potentiated by MAOIs.