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(PSYCHIATRIC TIMES) – Psychiatric disorders are common in the setting of malignant disease, occurring in almost 50% of patients. Many cancer patients cope well with their disease. For those who do not, untreated psychological and neuropsychiatric disorders can seriously compromise quality of life and treatment compliance. Although there is a wide variety of presentations, three behavioral syndromes that are often encountered in clinical practice will be discussed here: depression, anxiety, and delirium. Depression "Depression" exists on a continuum ranging from an emotion common in daily life (sadness) to a syndrome of severe physical and psychological symptoms consistent with a defined psychiatric disorder (major depressive disorder). In cancer patients, identical symptoms may be caused or influenced by physical (eg, tumor site, pain), psychological (eg, stress, premorbid function, maturity), and social (eg, finances, interpersonal relationships) factors. Depression occurs more frequently in the setting of severe illness; several studies of cancer inpatients report a prevalence of 25%-42%. SIGNS AND SYMPTOMS/DIAGNOSIS
Patients with depressive syndromes experience specific symptoms that vary in intensity and severity. 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, change in appetite, loss of libido, fatigue, diminished concentration, and psychomotor agitation or withdrawal. Focus of diagnostic evaluation Although the diagnosis of major depressive disorder requires that multiple symptoms (including dysphoria or anhedonia) must be present for at least 2 weeks, patients who do not meet these criteria may be in significant distress. The diagnosis of depression in medically ill patients is complicated by the fact that somatic symptoms of depression may also be caused by factors related to disease and treatment. For this reason, when evaluating the depressed cancer patient, special attention should be paid to psychological symptoms, which are less likely to be directly related to treatment. ETIOLOGY Psychological causes
Isolated symptoms Isolated depressive symptoms, if temporally related to an identifiable stressor, may be classified as adjustment disorders. In the setting of malignancy, obvious stressors include the initial diagnosis, treatment failure, or disease progression. Patients may also face potential psychosocial stressors, including changes in independence, body image, finances, and family function, as well as issues related to death and dying. Persistent symptoms Persistent mood symptoms may indicate the presence of an evolving major depressive disorder. 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. Disease- and treatment-related causes
Presenting symptom of malignancy Depression may be a presenting symptom of some primary malignancies, including primary pancreatic and gastric carcinomas. Primary and metastatic brain tumors may cause frontal lobe 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, antihypertensives, barbiturates, opioids, and benzodiazepines. In contrast, few drugs used as primary and supportive therapies for cancer are commonly associated with depression. The exceptions to this rule are corticosteroids, cytokines (especially interferon-alfa [IFN-α Intron A, Roferon- A] and interleukin-2 [aldesleukin, Proleukin]), and whole-brain radiation therapy. Depressive syndromes may also be seen with certain chemotherapeutic agents, including asparaginase (Elspar) and procarbazine (Matulane). Patients treated with tamoxifen may complain of depression or "chemobrain." The latter term usually refers to cognitive slowing. Day and colleagues have shown a lack of association between tamoxifen treatment and depression, even in women at higher risk for mood disorders. MANAGEMENT
Management of depressive syndromes involves accurate diagnosis, use of antidepressant medication, and psychotherapy. Patients should be assessed for somatic and psychological symptoms of depression. The clinician should always ask about suicidal thoughts or intent. Metabolic and thyroid function should be evaluated and medications reviewed. The decision to treat depression is a matter of clinical judgment. If mood disorder symptoms adversely affect quality of life, work or family relationships, or ability to participate in cancer therapy, intervention is indicated. Because the diagnosis of depression can be difficult to make in patients with cancer, it is best to have a low threshold for the initiation of treatment to minimize the risk of missing a reversible disorder

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. There is some anecdotal evidence that a more rapid effect is seen in cancer patients. As a general rule, antidepressant therapy should continue for 4-6 months after symptoms stabilize. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac, Sarafem), sertraline (Zoloft), paroxetine (Paxil), and escitalopram (Lexapro), are often used in patients with cancer because of their benign sideeffect profile. In particular, their lack of anticholinergic and α-adrenergic-blocking properties makes them attractive options for patients with a serious medical illness. Unlike the tricyclic agents (discussed below), the SSRIs are not lethal in overdose, making them a safe choice in the treatment of patients experiencing suicidal ideations. Side effects Mild nausea and anxiety are common side effects of all SSRIs, which vary in severity from patient to patient. Sexual dysfunction may occur with fluoxetine and paroxetine. Sedation may occur with paroxetine. Dosage In ambulatory patients with normal metabolic function, SSRIs can be started at the same doses used in general psychiatry (ie, 20 mg/d qAM for fluoxetine, 50 mg/d qAM for sertraline, 20 mg/d qAM for paroxetine). These doses can be increased if there is no response within 2-3 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. Tricyclic antidepressants (TCAs) These older antidepressants (eg, amitriptyline, nortriptyline, and desipramine) remain effective options for the treatment of depression in cancer patients. The sedative properties of TCAs can be useful in the treatment of insomnia associated with depression.

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