Depression in Cancer Patients

Drs. Jeremy Winell and Andrew Roth have provided a nice overview of the diagnosis and treatment of depression in cancer patients. The views they express are both widely accepted and applicable to other serious medical illnesses as well. They remind us of the challenge of making a valid diagnosis of depression in cancer patients, since all of the somatic symptoms of depression (eg, anorexia, fatigue, insomnia) may in some patients represent symptoms of cancer or cancer treatment rather than depression. Four Different Approaches
The authors briefly note four different potential solutions to this problem, the inclusive, etiologic, substitutive, and exclusive approaches. These alternatives have been discussed for a long time, and not just with cancer; this was recognized as a diagnostic problem in the presence of many medical illnesses.[1,2] None of the four solutions is ideal. The inclusive approach-in which one applies all of the criteria for depression, including the somatic ones, regardless of the apparent cause of symptoms- leads to overdiagnosis of depression, and presumably overtreatment. The etiologic approach is conceptually the most appealing, as one tries to determine whether a somatic symptom has been caused by depression, cancer, or cancer treatment. This is straightforward when there is a clearcut temporal relationship between a symptom and an event, but when illness, treatment, and mood disturbance overlap, it is difficult-if not impossible- to assign causation with any certainty. The exclusive approach, in which one excludes somatic symptoms of depression and uses only the psychological symptoms, risks underdiagnosing depression. This is particularly true in patients who are emotionally unexpressive, either because of temperament, personality, or culture. Finally, as Drs. Winell and Roth note, in the substitutive approach, one replaces the somatic symptoms of depression with additional emotional symptoms such as indecisiveness, hopelessness, and pessimism. However, this approach may overdiagnose psychiatric depression in patients whose psychological symptoms represent normal emotional responses to overwhelming illness, yet at the same time may miss the diagnosis of depression in patients whose depression is primarily manifested in somatic symptoms. So what is a clinician to do? Depending on the particularities of each individual case, experienced clinicians draw on all four of these approaches to varying degrees. The best place to start, as the authors suggest, is to ask patients if they consider themselves to be depressed. Asking about anhedonia has also been found to be very helpful in screening for depression, ie, asking patients if they are able to derive any pleasure or satisfaction from anything (though this question may be inappropriate during acute physical suffering) Suicidality Assessment
Drs. Winell and Roth remind readers that asking about suicidality is important. It is important both because its presence provides strong support for a diagnosis of depressive illness, and because it is crucial to identify those at risk in order to prevent suicide. The authors particularly urge assessment for suicidal thoughts and the desire for hastened death in the palliative care setting. It is true, as they note, that depression is a strong predictor of desire for hastened death in cancer patients, but the desire for hastened death is not synonymous with suicidal ideation, and also occurs in the absence of self-reported depression.[3] In my experience, it is usually possible to distinguish those patients who have tired of fighting an overwhelming illness that is either terminal or has left them with a permanently unacceptable quality of life, and who have therefore decided they no longer wish further treatment, from those patients who are seriously and actively contemplating taking their own lives through overdose, firearms, or other directly lethal means. The latter are suicidal, the former are not. Timing, Proportionality, and Context
Drs. Winell and Roth appropriately note that clinical depression should be distinguished from normal reactions, adjustment disorders, and medically caused symptoms. They note that the timing of symptoms is important in distinguishing normal reactions, ie, intense but normal disturbance in mood may follow receipt of bad news or the development of debilitating symptoms, and may last for a few weeks. In addition to timing, however, clinicians should consider proportionality and context. Are a patient's emotional symptoms out of proportion to those the clinician has come to expect as typical in similar patients? What one would expect as normal in intensity and in persistence depends on context. For example, one could reasonably expect quite different nor- mal reactions to a new diagnosis of metastatic colon cancer in an 85-yearold widow in a nursing home with debilitating arthritis vs an otherwise healthy 28-year-old woman who is pregnant with her first child. Pharmacologic Treatment Options
I have a few clarifications regarding treatment. While some antidepressants are available in liquid or dissolvable tablet form, they cannot be utilized in patients who are strictly npo, such as those with severe stomatitis from chemotherapy or radiation therapy. Intravenous antidepressants are not available in the United States. There are a number of anecdotal reports of the administration of antidepressants via rectal suppository, but their preparation is labor-intensive and data regarding the reliability of absorption are limited.[4] Drs. Winell and Roth are correct that some selective serotonin reuptake inhibitors, or SSRIs (sertraline [Zoloft], citalopram [Celexa], and escitalopram [Lexapro]), have less potential for P450 drug interactions than other SSRIs, but this is not because they are "less protein bound"; the reason is differences in which P450 subsystem enzymes are involved in their metabolism. Although the authors' statement that bupropion is contraindicated in patients with seizure disorders or those at risk "such as those with central nervous system disorders or eating disorders," is consistent with the Physician's Desk Reference and many textbooks, therapeutic doses of bupropion are not associated with a significant increase in seizures compared to other antidepressants.[4] The authors seem to suggest that the new antidepressant duloxetine (Cymbalta) should be reserved for treatment of pain syndromes. While duloxetine has also been approved by the US Food and Drug Administration for diabetic peripheral neuropathy pain, its primary indication is the treatment of depression. As the authors note, psychostimulants may be the preferred treatment for depression in the terminally ill. Their therapeutic benefit begins immediately, in contrast to the weeks required for traditional antidepressants. Unfortunately, some clinicians still avoid prescribing stimulants because they fear the risk of abuse or addiction. This concern is an inappropriate reason for withholding psychostimulants in the terminally ill, as it is for withholding opioid analgesics. The preferred choices are methylphenidate, dextroamphetamine, or the mixed amphetamine salt preparation marketed as Adderall. The authors mention the growing popularity of modafinil (Provigil), but it should also be noted that it is extremely expensive, and that there is no evidence that modafinil possesses efficacy superior to other stimulants. The Utility of Psychotherapy
Drs. Winell and Roth briefly mention the utility of psychotherapy. Readers should be aware that there is considerable empirical support based on controlled trials for the benefits of psychotherapy in cancer patients, including improvements in mood, vigor, and pain control. While most such trials have not been specifically in cancer patients with major depression, psychotherapy should be considered as more than an adjunctive treatment to combine with antidepressants. Some patients would prefer to utilize it as a primary treatment for their depression, which is certainly appropriate for mild to moderate depressions. Electroconvulsive Therapy
Finally, the authors do not mention electroconvulsive therapy (ECT), which remains the treatment of choice for some patients with severe depression, including many of those with psychotic symptoms, severe acute suicidality, or who do not respond to treatment with antidepressants. Although it is commonly believed that an intracranial tumor is an absolute contraindication, ECT has been reported to be used safely and effectively in a number of cases of patients with primary or metastatic brain tumor, although none of the patients had focal neurologic findings, increased intracranial pressure, or papilledema. In the presence of increased intracranial pressure or acute focal signs, there may be significant increased risk; ECT should be considered only when no other reasonable option exists.[5]