Antidepressant Agents
TCAs (eg, amitriptyline, doxepin, imipramine, nortriptyline, and desipramine) have been used frequently in the cancer setting. TCAs should be started at a low dose (10-25mg at bedtime) and increased slowly by 10- to 25-mg increments every 1-2 days until beneficial effect is achieved. This is especially important for debilitated patients with advanced disease. Cancer patients may exhibit a therapeutic response to the TCAs at lower doses than are required for physically healthy individuals.[15] Serial plasma drug levels can be utilized to monitor the effective and safe administration of the antidepressants, minimizing the risk of side effects or toxicity.[41] In addition, before TCAs are prescribed for cancer patients, it is recommended that a cardiac history and an ECG be obtained, as TCAs can have an adverse effect on cardiac rhythm.[42]
SSRIs (eg, fluoxetine, bupropion, trazodone, sertraline, paroxetine) have become the most widely used agents within the past few years. Their efficacy and side-effect profiles make them attractive agents for patients with cancer. Problems with cardiac arrhythmias, hypotension, and anticholinergic effects are minimized with the use of this group of drugs. Generally, the SSRIs have fewer sedative and autonomic effects than the TCAs, but since all of these drugs are strongly protein-bound, consideration must be given to their ability to increase blood levels of coumadin, digoxin, and cisplatin.
The psychostimulants (methylphenidate, dextroamphetamine, and pemoline) offer an alternative for depressed patients with cancer.[43,44] Psychostimulants have been shown to improve attention span, concentration, and overall performance on neurologic testing in the medically ill.[45] Mood, appetite, and sense of well-being can be improved for the patient at the same time the medication is decreasing feelings of weakness and fatigue. Most patients respond quickly to these agents, and if taken in the morning and early afternoon they should not interfere with sleep. Starting doses for methylphenidate and dextroamphetamine are 5-10mg qd or bid. Typically, patients are maintained on the stimulant for 1 to 2 months, or longer if necessary. Tolerance may develop, and dose-adjustment may be necessary. Side effects of stimulants are anxiety, overstimulation, insomnia, increase in blood pressure, and tremors, but these are rarely a problem with the typically low doses used in cancer patients. An additional benefit of methylphenidate and dextroamphetamine is their demonstrated effectiveness in reducing the sedation that is secondary to opioid analgesics and in providing adjuvant analgesia in cancer patients.[46]
Pemoline has the advantage of having more mild sympathomimetic effects. This agent comes in a chewable tablet form that can be absorbed through the buccal mucosa, potentially making it a good choice for cancer patients who have difficulty swallowing or those with intestinal obstruction. Pemoline's efficacy for the treatment of depressive symptoms has been clinically demonstrated.[47] Doses start at 18.75mg bid (8AM and 12 noon) and are increased gradually to a typical dose of 75mg/day. Pemoline should be used with caution in patients with liver impairment, and liver function tests should be monitored periodically with long-term treatment.
Combined antidepressant therapy may provide certain advantages to patients. Particularly directed at patients experiencing distressing physical symptoms, this approach promotes the use of supplemental antidepressant agents to improve relief of physical symptoms while adding to the overall antidepressant treatment. Patients with depression and severe fatigue or psychomotor slowing may gain the most from the use of TCAs or SSRIs and psychostimulants used together (ie, fluoxetine in low doses in the morning and nortriptyline at bedtime) or stimulants in the morning and a TCA at bedtime. Patients with depression and anxiety or insomnia may gain the most from a combination of TCAs and SSRIs. Since most antidepressants require a few weeks to reach their peak efficacy, the augmentation of another medication directed at the most distressing symptom not only provides a quicker benefit to the patient but, in turn, may also improve compliance with treatment. This symptom-driven approach may be particularly favorable in the treatment of cancer patients with advanced disease, in whom treatment is often complex, but for whom immediate symptom-distress relief needs to be a priority.
Medscape Psychiatry & Mental Health eJournal. 1997;2(3) © 1997 Medscape
Cite this: Depression in Cancer Patients: Recognition and Treatment - Medscape - May 22, 1997.
