An elderly man with metastatic lung cancer presented to the palliative care service with a request to die. He had become wheelchair bound and was no longer able to enjoy many previously pleasurable and meaningful activities. A person who previously was "always in control," he now found himself constantly crying and thinking about the futility of living and a wish for death. He was burdened with feelings of guiltspecifically that he had become a burden to his family and care providers. Within 3 weeks of antidepressant therapy and supportive counseling, his depressive symptoms remitted entirely, allowing him to enjoy spending time with his wife, who helped nurse him through his final days.
Many antidepressant medications are available (see Table 1), and a number of factors should be considered when choosing a medication. For example, antidepressants that may take 4 to 8 weeks to achieve a therapeutic effect are a poor choice for patients with days or weeks to live. In such cases, psychostimulants, which are more rapidly acting, may be a better alternative.
Overall side-effect profile and tolerability are essential considerations. If the patient has been successfully treated for depression in the past, first consideration should be given to using the same medication for treatment of the current episode. When treating older patients, changes in drug metabolism, such as reduced gut absorption, altered drug distribution (loss of lean body mass with increased half-life of lipophilic medication), and reduced metabolism and excretion, should be kept in mind. Poor nutritional status can cause reduced albumin levels, which will increase the proportion of unbound (active) antidepressant medication.
For patients who are antidepressant-naive, it is worthwhile to determine whether there is a first-degree relative who has been successfully treated with a particular antidepressant. That same medication should be given first consideration, other things being equal. When psychotic features such as hallucinations, delusions, or grossly disorganized thinking are present, patients should be treated with both an antidepressant and antipsychotic.
Although there is less experience with the new-generation (atypical) antipsychotics, low doses of this class of medication, such as risperidone(Drug information on risperidone) (Risperdal), olanzapine(Drug information on olanzapine) (Zyprexa), quetiapine (Seroquel), and ziprasidone(Drug information on ziprasidone) (Geodon), have a preferable side-effect profile compared to the older neuroleptics. Olanzapine may also stimulate appetite in cachectic patients.
Among older medications, higher-potency neuroleptics such as haloperidol(Drug information on haloperidol), trifluoperazine(Drug information on trifluoperazine), or fluphenazine(Drug information on fluphenazine) are usually preferable, as they have a lower incidence of anticholinergic side effects (eg, delirium, cardiac arrhythmias, constipation, urinary retention, and blurred vision). These drugs also tend to have less of an effect on the seizure threshold than lower-potency antipsychotics such as chlorpromazine(Drug information on chlorpromazine) and thioridazine. Finally, if there is a history of bipolar disorder, mood stabilizers (such as lithium(Drug information on lithium), sodium valproate(Drug information on valproate), or carbamazepine(Drug information on carbamazepine)) may be needed.[7,10]
Selective Serotonin-Reuptake Inhibitors
Selective serotonin-reuptake inhibitors (SSRIs) are generally well tolerated, effective, and preferred over tricyclic antidepressants (TCAs) in the cancer setting. Compared with TCAs, SSRIs are associated with a decreased incidence of anticholinergic side effects including orthostatic hypotension, and are less likely to cause tachycardia or arrhythmias. They appear to be relatively safe in overdose, although there are rare case reports of hyponatrenia due to syndrome of inappropriate diuretic hormone (SIADH) in geriatric patients, as well as occasional reports of hypomania.
More common side effects include transient gastrointestinal upset, insomnia, headaches, sexual dysfunction, and occasional agitation or anxiety. Side effects are dose-related, supporting the clinical adage "start low and go slow." SSRIs have a variable ability to inhibit the hepatic cytochrome P450 enzyme system, which is responsible for metabolizing numerous medications including the SSRIs themselves (see Table 2). In this regard, citalopram(Drug information on citalopram) (Celexa) is the "cleanest" of the SSRIs.
Serotonin Norepinephrine(Drug information on norepinephrine)-Reuptake Inhibitors
Venlafaxine (Effexor) is a potent inhibitor of both serontonin and norepinephrine reuptake, with a minor impact on muscarinic, histaminic, or alpha-adrenergic receptors. It may increase systolic blood pressure in some patients but is associated with few protein binding-induced drug interactions. Venlafaxine may cause nausea if the dose is started too high or increased too rapidly; other potential side effects include headache, dry mouth, sedation, and tremors. The appropriate dose varies according to studies, ranging from 18.75 to 300 mg/d.
Serotonin Antagonist-Reuptake Inhibitors
Nefazodone (Serzone) is associated with less sexual dysfunction than the SSRIs. Its sedating effect may also be helpful in depression-related sleep problems. The drug has a short half-life, minimal anticholinergic activity, and no apparent cardiotoxicity. Side effects include dry mouth, dizziness, sedation, gastrointestinal upset, and postural hypotension. The starting dose is 50 mg once or twice daily, with a therapeutic range of 200 to 600 mg/d.
The effective dose of trazodone200 to 600 mg/dis often so sedating as to preclude its usefulness. The drug may be used as a sedative hypnotic in doses of 25 to 100 mg, but it has been shown to be associated with arrhythmias in patients in the acute phase (ie, within 6 weeks) of a myocardial infarction. There have been rare reports of priapism, so male patients must be warned about this possible side effect.
Norepinephrine Dopamine(Drug information on dopamine) Modulators
A generally well tolerated drug, bupropion (Wellbutrin) has minimal interactions with other medications. Common side effects include dry mouth, headache, gastrointestinal upset, agitation, and insomnia. It has minimal effect on cardiac function but may cause small increases in blood pressure. Bupropion can slightly increase the risk of seizures (0.4%) in doses above 300 mg and should be used cautiously in patients with seizure disorders or central nervous system disorders. It has a stimulant-like effect, which is useful when significant psychomotor retardation is present.
Monoamine Oxidase Inhibitors
Monoamine oxidase inhibitors (MAOIs) are generally avoided, unless the patient has had a previous good response to these drugs predating their cancer treatment. They are associated with numerous problems. For instance, consumption of foods rich in tyramine or the use of sympathomimetic drugs such as pseudoephedrine(Drug information on pseudoephedrine) or psychostimulants with MAOIs can cause a potentially fatal hypertensive crisis. In combination with opioid analgesics, they may cause myoclonus and delirium. When combined with meperidine, MAOIs have been associated with death. Hence, they are rarely used in the depressed cancer patient.