Although many cancer patients cope well with their disease, psychiatric disorders occur in almost 50% of patients in the setting of malignancy. Untreated psychological and neuropsychiatric disorders can compromise quality of life as well as treatment compliance. Three behavioral syndromes that are often encountered in clinical practice will be discussed here: depression, anxiety, and delirium.

Depression

Sadness exists on a continuum, ranging from an emotion common in daily life to a syndrome of severe physical and psychological symptoms consistent with a defined psychiatric disorder (Major Depressive Disorder). Several studies of cancer inpatients report Major Depression prevalence rates of 25% to 42%.

SIGNS AND SYMPTOMS/DIAGNOSIS

Patients with depressive syndromes may experience an array of psychological and somatic symptoms.

Psychological symptoms include dysphoria (sadness), anhedonia (pervasive loss of pleasure in activities), feelings of guilt or low self-esteem, and thoughts of death or suicide.

Somatic symptoms include sleep disturbance (ie, sleeping too much or too little), change in appetite, fatigue, diminished concentration, and psychomotor agitation or withdrawal.

Focus of diagnostic evaluation Although the diagnosis of Major Depressive Disorder requires that greater than half of these symptoms (including dysphoria or anhedonia) be present for at least 2 weeks, patients who do not meet these criteria may be in significant distress, and may be described as having an Adjustment Disorder. In medically ill patients, diagnosis is complicated by the fact that somatic symptoms may also arise as a result of disease and treatment. For this reason, when evaluating the depressed cancer patient, special attention should be paid to those psychological symptoms that are less likely to be directly related to somatic disease or treatment.

ETIOLOGY

Psychological causes

Major depressive disorder is common in the general population (point prevalence, ~6%) and is a recurrent disease. Patients with a history of mood disorder are at risk for relapse in the face of a cancer diagnosis. In the setting of malignancy, obvious stressors include news of initial diagnosis, treatment failure, or disease progression. Patients may also confront more subtle stressors, including loss of independence, financial woes, diminished body image, family strain, and existential angst.

Disease- and treatment-related causes

Presenting symptom of malignancy Depression may be a presenting symptom of some primary malignancies, most notably pancreatic carcinoma. Primary and metastatic brain tumors can cause frontal lobe disinhibition syndromes or personality changes that mimic depression and other psychiatric disorders.

Drugs Many drugs used in general medical practice are associated with psychiatric syndromes. The most common of these drugs are β-blockers, anti-hypertensives, barbiturates, opioids, and benzodiazepines. Many primary and supportive therapies for cancer are also commonly associated with depression. They include corticosteroids (also possibly associated with mania), cytokines (especially interferon-alfa and interleukin-2), whole-brain radiation therapy, and chemotherapeutic agents, including procarbazine (Matulane). Patients treated with tamoxifen may complain of depression or “chemo brain.” The latter term usually refers to cognitive slowing. Treatment of tamoxifen-related depression raises particular challenges. Recent evidence suggests that many antidepressants used to treat these symptoms inhibit tamoxifen’s anti-cancer effect through P450 interactions.

MANAGEMENT

Management of depressive syndromes begins with accurate diagnosis. Clinicians should assess for somatic and psychological symptoms of the syndrome and should always ask about suicidal thoughts or intent. In addition to medication, laboratory assessments should be reviewed, as metabolic disarray, anemia, low B12 levels, and thyroid dysfunction can all contribute to the development of depressive symptoms. Once depression is diagnosed, treatment involves antidepressant medication, sleep aids, when possible, removal of exacerbating agents, and psychotherapy.

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 (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), paroxetine, and 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 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.