Purpose of This PDQ Summary
Overview
Assessment and Diagnosis

Symptoms and Risk Factors Screening and Assessment for Depression         Clinical interview Diagnosis

Intervention

Pharmacologic Intervention         Overview         Suicide risk of antidepressant medication         Interferon-related depression         Antidepressant medication selection         Selective serotonin reuptake inhibitors         Discontinuation of antidepressants         Side effects         Drug-drug interactions         Atypical antidepressants         Benzodiazepines         Psychostimulants         Monoamine oxidase inhibitors         St. John's wort         Antidepressant effects Psychotherapy         Overview         Empirical studies of the efficacy of psychotherapy

Suicide Risk in Cancer Patients

Demographics and Statistics Etiology/Pathophysiology

Assessment, Evaluation, and Management of Suicidal Patients

Assessment Management Effect on Family and Health Care Providers Assisted Dying, Euthanasia, Decisions Regarding End of Life

Pediatric Considerations for Depression

Assessment and Diagnosis of Pediatric Depression         Assessment         Diagnosis Management of Pediatric Depression         Pharmacologic management

Pediatric Considerations for Suicidality

Incidence Etiology/Assessment Management Pharmacologic Management

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Changes to This Summary (10/24/2008)
Questions or Comments About This Summary
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Purpose of This PDQ Summary

This PDQ cancer information summary provides comprehensive, peer-reviewed information for health professionals about cancer-related depression and suicide risk in both the adult and the pediatric population. This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board.

Information about the following is included in this summary:

• Assessment.
• Diagnosis.
• Management.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients during and after cancer treatment. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version, which is written in less technical language, and in Spanish.

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Overview

Depression is a comorbid disabling syndrome that affects approximately 15% to 25% of cancer patients.[1-4] Depression is believed to affect men and women with cancer equally, and gender-related differences in prevalence and severity have not been adequately evaluated.[5] Individuals and families who face a diagnosis of cancer will experience varying levels of stress and emotional upset. Depression in patients with cancer not only affects the patients themselves but also has a major negative impact on their families. A survey in England of women with breast cancer showed that among several factors, depression was the strongest predictor of emotional and behavioral problems in their children.[6] Fear of death, disruption of life plans, changes in body image and self-esteem, changes in social role and lifestyle, and financial and legal concerns are significant issues in the life of any person with cancer, yet serious depression or anxiety is not experienced by everyone who is diagnosed with cancer.

Just as patients require ongoing evaluation for depression and anxiety throughout their course of treatment, so do family caregivers. In a study of family caregivers of patients in the palliative phase of illness, both male and female caregivers experienced significantly more anxiety than normal samples, while there was an increased incidence of Hospital Anxiety and Depression Scale–defined depression among women.[7]

There are many myths about cancer and how people cope with it, such as the following:

• All people with cancer are depressed.
• Depression in a person with cancer is normal.
• Treatments are not helpful.
• Everyone with cancer faces suffering and a painful death.

Sadness and grief are normal reactions to the crises faced during cancer. All people will experience these reactions periodically. Because sadness is common, it is important to distinguish between normal degrees of sadness and depressive disorders. An end-of-life consensus panel review article describes details regarding this important distinction and illustrates the major points using case vignettes.[8] A critical part of cancer care is the recognition of the levels of depression present and determination of the appropriate level of intervention, ranging from brief counseling or support groups to medication and/or psychotherapy. For example, relaxation and counseling interventions have been shown to reduce psychological symptoms in women with a new diagnosis of gynecological cancer.[9] Some people may have more difficulty adjusting to the diagnosis of cancer than others and will vary in their responses to the diagnosis. Major depression is not simply sadness or a blue mood. Major depression affects approximately 25% of patients and has recognizable symptoms that can and should be diagnosed and treated because they have an impact on quality of life.[10,11] Depression is also an underdiagnosed disorder in the general population. Symptoms evident at the time of a cancer diagnosis may represent a preexisting condition and warrant separate evaluation and treatment.

Depression and anxiety disorders are common among patients receiving palliative care and contribute to a greatly diminished quality of life in these patients.[12] In the Canadian National Palliative Care Survey, patients receiving palliative care for cancer (n = 381) were evaluated for depressive and anxiety disorders and for the impact of these disorders on quality of life. The primary assessment tool was a modified version of the Primary Care Evaluation of Mental Disorders (PRIME-MD). A significant number of participants (24.4%; 95% confidence interval, 20.2–29.0) were found to fulfill diagnostic criteria for at least one depressive or anxiety disorder (20.7% prevalence for depressive disorder and 13.1% for anxiety disorder). Participants diagnosed with a disorder were significantly younger than the other participants (P = .002), had lower performance status (P = .017), had smaller social networks (P = .008), and participated less in organized religious services (P = .007). They also reported more severe distress about physical symptoms, social concerns, and existential issues, suggesting significant negative impact on other aspects of their quality of life.[12]

Normally, a patient's initial emotional response to a diagnosis of cancer is brief, extending over several days to weeks, and may include feelings of disbelief, denial, or despair. This normal response is part of a spectrum of depressive symptoms that range from normal sadness to adjustment disorder with depressed mood to major depression.[8] Other syndromes described include dysthymia and subsyndromal depression (also called minor depression or subclinical depression). Dysthymia is a chronic mood disorder in which a depressed mood is present on more days than not for at least 2 years. In contrast, subsyndromal depression is an acute mood disorder that is less severe (some, but not all, diagnostic symptoms present) than major depression.

The emotional response to a diagnosis of cancer (or cancer relapse) may begin as a dysphoric period marked by increasing turmoil. The individual will experience sleep and appetite disturbance, anxiety, ruminative thoughts, and fears about the future. Epidemiologic studies, however, suggest that at least one half of all people diagnosed with cancer will successfully adapt. Markers of successful adaptation include maintaining active involvement in daily life; minimizing the disruptions caused by the illness to one's life roles (e.g., spouse, parent, employee); regulating the normal emotional reactions to the illness; and managing feelings of hopelessness, helplessness, worthlessness, and/or guilt.[13] As shown by a study of adult cancer patients (n = 48) and their adult relatives (n = 99), family functioning is an important factor that impacts patient and family distress. Families that were able to act openly, express feelings directly, and solve problems effectively had lower levels of depression, and direct communication of information within the family was associated with lower levels of anxiety.[14] Recent studies suggest an association between maladaptive coping styles with higher levels of depression, anxiety, and fatigue symptoms.[15,16] Examples of maladaptive coping behaviors include avoidant or negative coping, negative self-coping statements, preoccupation with physical symptoms, and catastrophizing. One study conducted in a group of 86 mostly late-stage cancer patients suggested that maladaptive coping styles and higher levels of depressive symptoms are potential predictors of the timing of disease progression.[16] Another study examining coping strategies in women with breast cancer (n = 138) concluded that patients with better coping skills such as positive self-statements have lower levels of depressive and anxiety symptoms.[15] The same study found racial differences in the use of coping strategies, with African American women reporting and benefiting more from the use of religious coping strategies such as prayer and hopefulness than did Caucasian women.[15] Preliminary data suggest a beneficial impact of spirituality on associated depression, as measured by the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being (FACIT-Sp) and the Hamilton Depression Rating Scale.[17] The following indicators may suggest a need for early intervention: a history of depression, a weak social support system (not married, few friends, a solitary work environment), evidence of persistent irrational beliefs or negativistic thinking regarding the diagnosis, a more serious prognosis, and greater dysfunction related to cancer.

Cancer-related depression is not substantially different from depression in other medical conditions, but treatments may need to be adapted or refined for cancer patients.[18] When the clinician begins to suspect that a patient is depressed, he or she will assess the patient for symptoms. Mild or subclinical levels of depression that include some, but not all, of the diagnostic criteria for a major depressive episode can cause considerable distress and may warrant interventions such as supportive individual or group counseling, either by a mental health professional or through participation in a self-help support group.[19] Even in the absence of any symptoms, many patients express interest in supportive counseling, and clinicians should try to accommodate those patients by a referral to a qualified mental health professional. When symptoms are more intense, longer lasting, or recurrent after apparent resolution, however, treatment to alleviate symptoms is essential.[11,20,21] Anxiety and depression in early treatment are good predictors of these same problems at 6 months.[22] In a study of older women with breast cancer, a recent diagnosis of depression was associated with both a greater likelihood of not receiving definitive cancer treatment and poorer survival.[23]

The pathophysiology of cancer-related depression remains unclear and probably encompasses many mechanisms. A study of patients with advanced metastatic cancer showed that both plasma interleukin-6 (IL-6) concentrations and hypothalamic-pituitary-adrenal (HPA) axis dysfunction were markedly higher in patients with clinical depression.[24] A cut-off value of 10.6 pg/mL for IL-6 yielded a sensitivity of 79% and specificity of 87%, while a cut-off value of 33.5% for cortisol variations (VAR) yielded a sensitivity of 81% and specificity of 88%. One limitation of this study was that neither pain levels nor fatigue levels were measured, which might independently affect these relationships.

References

1. Henriksson MM, Isometsä ET, Hietanen PS, et al.: Mental disorders in cancer suicides. J Affect Disord 36 (1-2): 11-20, 1995.  [PUBMED Abstract]
   
   
2. Bodurka-Bevers D, Basen-Engquist K, Carmack CL, et al.: Depression, anxiety, and quality of life in patients with epithelial ovarian cancer. Gynecol Oncol 78 (3 Pt 1): 302-8, 2000.  [PUBMED Abstract]
   
   
3. Lloyd-Williams M, Friedman T: Depression in palliative care patients--a prospective study. Eur J Cancer Care (Engl) 10 (4): 270-4, 2001.  [PUBMED Abstract]
   
   
4. Derogatis LR, Morrow GR, Fetting J, et al.: The prevalence of psychiatric disorders among cancer patients. JAMA 249 (6): 751-7, 1983.  [PUBMED Abstract]
   
   
5. Miaskowski C: Gender differences in pain, fatigue, and depression in patients with cancer. J Natl Cancer Inst Monogr (32): 139-43, 2004.  [PUBMED Abstract]
   
   
6. Watson M, St James-Roberts I, Ashley S, et al.: Factors associated with emotional and behavioural problems among school age children of breast cancer patients. Br J Cancer 94 (1): 43-50, 2006.  [PUBMED Abstract]
   
   
7. Grov EK, Dahl AA, Moum T, et al.: Anxiety, depression, and quality of life in caregivers of patients with cancer in late palliative phase. Ann Oncol 16 (7): 1185-91, 2005.  [PUBMED Abstract]
   
   
8. Block SD: Assessing and managing depression in the terminally ill patient. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians - American Society of Internal Medicine. Ann Intern Med 132 (3): 209-18, 2000.  [PUBMED Abstract]
   
   
9. Petersen RW, Quinlivan JA: Preventing anxiety and depression in gynaecological cancer: a randomised controlled trial. BJOG 109 (4): 386-94, 2002.  [PUBMED Abstract]
   
   
10. Massie MJ, Holland JC: The cancer patient with pain: psychiatric complications and their management. Med Clin North Am 71 (2): 243-58, 1987.  [PUBMED Abstract]
    
    
11. Lynch ME: The assessment and prevalence of affective disorders in advanced cancer. J Palliat Care 11 (1): 10-8, 1995 Spring.  [PUBMED Abstract]
    
    
12. Wilson KG, Chochinov HM, Skirko MG, et al.: Depression and anxiety disorders in palliative cancer care. J Pain Symptom Manage 33 (2): 118-29, 2007.  [PUBMED Abstract]
    
    
13. Spencer SM, Carver CS, Price AA: Psychological and social factors in adaptation. In: Holland JC, Breitbart W, Jacobsen PB, et al., eds.: Psycho-oncology. New York, NY: Oxford University Press, 1998, pp 211-22. 
    
    
14. Edwards B, Clarke V: The psychological impact of a cancer diagnosis on families: the influence of family functioning and patients' illness characteristics on depression and anxiety. Psychooncology 13 (8): 562-76, 2004.  [PUBMED Abstract]
    
    
15. Reddick BK, Nanda JP, Campbell L, et al.: Examining the influence of coping with pain on depression, anxiety, and fatigue among women with breast cancer. J Psychosoc Oncol 23 (2-3): 137-57, 2005.  [PUBMED Abstract]
    
    
16. Beresford TP, Alfers J, Mangum L, et al.: Cancer survival probability as a function of ego defense (adaptive) mechanisms versus depressive symptoms. Psychosomatics 47 (3): 247-53, 2006 May-Jun.  [PUBMED Abstract]
    
    
17. Nelson CJ, Rosenfeld B, Breitbart W, et al.: Spirituality, religion, and depression in the terminally ill. Psychosomatics 43 (3): 213-20, 2002 May-Jun.  [PUBMED Abstract]
    
    
18. Patrick DL, Ferketich SL, Frame PS, et al.: National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002. J Natl Cancer Inst 95 (15): 1110-7, 2003.  [PUBMED Abstract]
    
    
19. Meyer TJ, Mark MM: Effects of psychosocial interventions with adult cancer patients: a meta-analysis of randomized experiments. Health Psychol 14 (2): 101-8, 1995.  [PUBMED Abstract]
    
    
20. Massie MJ, Holland JC: Overview of normal reactions and prevalence of psychiatric disorders. In: Holland JC, Rowland JH, eds.: Handbook of Psychooncology: Psychological Care of the Patient With Cancer. New York, NY: Oxford University Press, 1989, pp 273-82. 
    
    
21. Massie MJ, Shakin EJ: Management of depression and anxiety in cancer patients. In: Breitbart W, Holland JC, eds.: Psychiatric Aspects of Symptom Management in Cancer Patients. Washington, DC: American Psychiatric Press, 1993, pp 470-91. 
    
    
22. Nordin K, Glimelius B: Predicting delayed anxiety and depression in patients with gastrointestinal cancer. Br J Cancer 79 (3-4): 525-9, 1999.  [PUBMED Abstract]
    
    
23. Goodwin JS, Zhang DD, Ostir GV: Effect of depression on diagnosis, treatment, and survival of older women with breast cancer. J Am Geriatr Soc 52 (1): 106-11, 2004.  [PUBMED Abstract]
    
    
24. Jehn CF, Kuehnhardt D, Bartholomae A, et al.: Biomarkers of depression in cancer patients. Cancer 107 (11): 2723-9, 2006.  [PUBMED Abstract]
    
    

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Assessment and Diagnosis

Symptoms and Risk Factors

The symptoms of major depression are as follows:

• A depressed mood for most of the day and on most days.
• Diminished pleasure or interest in most activities.
• Significant change in appetite and sleep patterns.
• Psychomotor agitation or slowing.
• Fatigue.[1]
• Feelings of worthlessness or excessive, inappropriate guilt.
• Poor concentration.
• Recurrent thoughts of death or suicide.

Cognitive symptoms may express themselves as repeated and ruminative thoughts such as “I brought this on myself," "God is punishing me," or "I'm letting my family down,” and as fatalistic expectations concerning prognosis, despite realistic evidence to the contrary. Such thinking may predominate or may alternate with more realistic thinking, yet remain very stressful. Some individuals will share negativistic thoughts freely, and family members may be aware of them. Other patients will not volunteer such thinking but will respond to brief inquiries such as the following (other examples are listed in the Suggested Questions For the Assessment of Depressive Symptoms in Adults With Cancer table):

• “Many people find themselves dwelling on thoughts about their cancer. What kinds of thoughts do you have?”



• “Do you find yourself ever thinking I brought this on myself, God is punishing me? How often? Only a few times a week, or all the time? Do you believe these thoughts are true?”



• “In spite of these thoughts, are you still able to go on with your life and find pleasure in things? Or, are you so preoccupied that you can't sleep, or feel hopeless?”

It is possible for a physician or nurse to ask these types of questions without becoming engaged in providing counseling themselves. Merely asking these questions will express concern and increase the likelihood that the patient will be receptive to suggestions for further counseling.

A statement such as the following can then follow these questions:

“Many people with cancer sometimes have these feelings. You are not alone. But talking to someone else about them can greatly help. I'd like to suggest that you consider doing that. Would you be willing to talk to someone who has a lot of experience helping people cope with the stress of having cancer?”

It is preferable at this time both to encourage the patient to seek out someone already known to him or her and to inform him or her of other resources in the community. Particularly for patients who have completed cancer treatment and who have manageable physical symptoms, higher perceived availability of social support has been associated with fewer depressive symptoms.[2] In some instances, referral to a clergy person or therapist may also be appropriate. Most therapists can address general issues of grief or fears about death; some will specialize in clinical health psychology, medical social work, or even working primarily with cancer patients. For the hesitant patient, suggesting multiple resources will increase the likelihood that some assistance will be sought. For other patients, a formal direct referral may be appropriate.

Evaluation of depression in people with cancer should include careful assessment of symptoms, treatment effects, laboratory data results, physical status, and mental status. Although the etiology of depression is largely unknown, many risk factors for depression are known (see list below). Limited data suggest that depressive symptomatology in cancer patients undergoing cytokine therapy with interferon-alfa and interleukin-2 may be mediated by changes in availability of neurotransmitter precursors.[3] For patients with head and neck cancer treated with curative intent, 8 pretreatment variables (tumor stage, sex, depressive symptoms, openness to discuss cancer in the family, perceived available support, received emotional support, tumor-related symptoms, and size of the informal social network) can be used to predict which patients are likely to become depressed up to 3 years after treatment.[4,5] A prospective study of terminally ill Japanese patients who were assessed for psychiatric illness by structured clinical interview at the time of registration (baseline) and again at admission to a palliative care unit (follow-up) found that 5 (42%) of the 12 patients diagnosed with adjustment disorder at baseline progressed to major depression at follow-up. Only the Hospital Anxiety and Depression Scale was significantly predictive of psychiatric diagnoses at follow-up.[6] Heightened awareness of this facilitates early diagnosis and the use of appropriate interventions.[7] For some cancer populations, such as those status-post stem cell transplantation, preliminary data suggest an association between depressive symptoms and survival. If confirmed, diagnosis and treatment of depression may afford an opportunity to impact mortality as well as quality of life.[8] In the medically ill, early manifestations of delirium may be mistaken for anxiety or depression. These disorders should be considered among the differential diagnoses in individuals who present with depressive symptoms.

Risk Factors for Depression in People With Cancer

• Cancer-related risk factors:
  • Depression at time of cancer diagnosis.[9,10]
  • Poorly controlled pain.[11]
  • Advanced stage of cancer.[11]
  • Increased physical impairment or discomfort.
  • Pancreatic cancer.[12]
  • Being unmarried and having head and neck cancer.[13]
  • Treatment with certain chemotherapeutic agents:
    • Corticosteroids.
    • Procarbazine.
    • L-Asparaginase.
    • Interferon-alfa.[14,3]
    • Interleukin-2.[15,14,3]
    • Amphotericin-B.



• Noncancer-related risk factors:
  • History of depression:
    • Two or more episodes in a lifetime.
    • First episode early or late in life.
  • Lack of family support.[9]
  • Additional concurrent life stressors.[16]
  • Family history of depression or suicide.
  • Previous suicide attempts.
  • History of alcoholism or drug abuse.
  • Concurrent illnesses that produce depressive symptoms (i.e., stroke or myocardial infarction).
  • Past treatment for psychological problems.[17]

Because of the common underrecognition and undertreatment of depression in people with cancer, screening tools can be used to prompt further assessment.[18] Among the physically ill, in general, instruments used to measure depression have not been shown to be more clinically useful than an interview and a thorough examination of mental status. Simply asking the patient whether he or she is depressed may improve the identification of depression. In persons with advanced cancer, a single-item interview question has been found to have acceptable psychometric properties and can be useful. One example is to ask “Are you depressed?”[19] Another example is to say, “Please grade your mood during the past week by assigning it a score from 0 to 100, with a score of 100 representing your usual relaxed mood.” A score of 60 is considered a passing grade.[20] Other screening tools that have been used and validated in cancer populations include the Hospital Anxiety and Depression Scale,[21] the Psychological Distress Inventory,[22] and the Edinburgh Depression Scale.[23] The Hospital Anxiety and Depression Scale may have limited utility in certain patient populations such as early-stage breast cancer [24] and palliative care.[25,26] The Brief Symptom Inventory, the Zung Self-Rating Depression Scale, and the Distress Thermometer are commonly used screening tools.[27-29] One study of women with newly diagnosed breast cancer (n = 236) successfully utilized brief screening instruments such as the Distress Thermometer and the Patient Health Questionnaire (PHQ-9) to identify women requiring further assessment to detect clinically significant levels of distress and psychiatric symptoms.[30] A modification of the Distress Thermometer, the Impact Thermometer, to be used in combination with the Distress Thermometer, has improved specificity for the detection of adjustment disorders and/or major depression, as compared with the Distress Thermometer. The revised tool has a screening performance comparable to that of the Hospital Anxiety and Depression Scale and is brief, potentially making it an effective tool for routine screening in oncology settings.[31] The Mood Evaluation Questionnaire, a cognitive-based screening tool for depression, has moderate correlation with the structured clinical interview for DSM-III-R and good acceptability in the palliative care population. With further validation, it may become a useful alternative in this population because it can be used by clinicians who are not trained in psychiatry.[32]

It is important that screening instruments be validated in cancer populations and used in combination with structured diagnostic interviews.[33] A pilot study of 25 patients used a simple, easily reproduced visual analog scale suggesting the benefits to a single-item approach to screening for depression. This scale consists of a 10-cm line with a sad face at one end and a happy face at the other end, on which patients make a mark to indicate their mood. Although the results do suggest that a visual analog scale may be useful as a screening tool for depression, the small patient numbers and lack of clinical interviews limit conclusions. Furthermore, although very high correlations with the Hospital Anxiety and Depression Scale were reported (r = 0.87), no indication of cut-offs was given. Finally, it should be emphasized that such a tool is intended to suggest the need for further professional assessment. However, if validated further, this simple approach could greatly enhance assessment and management of depression in cognitively intact advanced cancer patients.[34,7] Other brief assessment tools for depression can be used. To help patients distinguish normal anxiety reactions from depression, assessment should include discussion about common symptoms experienced by cancer patients. Depression should be reassessed over time.[35] Because of the increased risk of adjustment disorders and major depression in cancer patients, routine screening with increased vigilance at times of increased stress (i.e., diagnosis, recurrences, progression) is recommended. General risk factors for depression are noted in the list above. Other risk factors may pertain to specific populations, i.e., patients with head and neck cancer [4] and women at high risk for the development of breast cancer.[36]

Organic Mood Syndromes or Mood Syndromes Related to Medical Condition (MSRMC), as they are now referred to in the Diagnostic and Statistical Manual for Mental Disorders, 4th Edition (DSM-IV), often mimic the mood syndromes in their presentation. The assumption is made (perhaps based on their time course or laboratory data) that an organic or medical factor has a role in the etiology of the syndrome. The DSM-IV suggests that prominent cognitive abnormalities may be accompanying factors and therefore are useful in making the diagnosis. The DSM-IV also highlights profound apathy as a sign of MSRMC. Consideration should be given to obtaining laboratory data to assist in detection of electrolyte or endocrine imbalances or the presence of nutritional deficiencies. Clinical experience suggests that pharmacotherapy is more advantageous than psychotherapy alone in the treatment of depression that is caused by medical factors, particularly if the dosages of the causative agent(s), i.e., steroids, antibiotics, or other medications, cannot be decreased or discontinued.[38]

Possible Medical Causes of Depressive Symptoms in People With Cancer*

• Uncontrolled pain.[11]
• Metabolic abnormalities:
  • Hypercalcemia.
  • Sodium/potassium imbalance.
  • Anemia.
  • Vitamin B12 or folate deficiency.
  • Fever.
• Endocrine abnormalities:
  • Hyperthyroidism or hypothyroidism.
  • Adrenal insufficiency.
• Medications:[15,39-41,3]
  • Steroids.
  • Endogenous and exogenous cytokines, i.e., interferon-alfa and aldesleukin (interleukin-2, IL-2).[42]
  • Methyldopa.
  • Reserpine.
  • Barbiturates.
  • Propranolol.
  • Some antibiotics (e.g., amphotericin B).
  • Some chemotherapeutic agents (e.g., procarbazine, L-asparaginase).

To make a diagnosis of depression, the clinician should confirm that these symptoms will have lasted a minimum of 2 weeks and are present on most days. The diagnosis of depression in people with cancer can be difficult due to the problems inherent in distinguishing biological or physical symptoms of depression from symptoms of illness or toxic side effects of treatment. This is particularly true of individuals who are receiving active treatment or those with advanced disease. Cognitive symptoms such as guilt, worthlessness, hopelessness, thoughts of suicide, and loss of pleasure in activities are probably the most useful in diagnosing depression in people with cancer. One German study comparing cancer patients who had a current affective disorder with those who had a single depressive symptom found loss of interest, followed by depressed mood, to yield the highest power of discrimination between the two groups on multivariate analysis.[43]

The evaluation of depression in people with cancer should also include a careful assessment of the person's perception of the illness, medical history, personal or family history of depression or thoughts of suicide, current mental status, and physical status, as well as treatment and disease effects, concurrent life stressors, and availability of social supports. It is important to understand that more than 90% of patients indicate that they prefer to discuss emotional issues with their physician, but over one quarter of patients feel that the physician must initiate any discussion of that topic.[44] Suicidal ideation, when it occurs, is frightening for the individual, the health professional, and the family. Suicidal statements may range from an offhand comment resulting from frustration or disgust with a treatment course: “If I have to have one more bone marrow aspiration this year, I'll jump out the window,” to a reflection of significant despair and an emergent situation: “I can no longer bear what this disease is doing to all of us, and I am going to kill myself.” Exploring the seriousness of the thoughts is imperative. If the suicidal thoughts are believed to be serious, a referral to a psychiatrist or psychologist should be made immediately and attention should be given to the patient's safety. Additional information on suicide can be found in the Suicide Risk in Cancer Patients section.

The most common form of depressive symptomatology in people with cancer is an adjustment disorder with depressed mood, sometimes referred to as reactive depression. This disorder is manifested when a person has a dysphoric mood that is accompanied by the inability to perform usual activities.[45] The symptoms appear to be prolonged and in excess of a normal and expected reaction but do not meet the criteria for a major depressive episode. When these symptoms significantly interfere with a person's daily functioning, such as attending to work or school activities, shopping, or caring for a household, they should be treated in the same way that major depression is treated (i.e., consider using crisis intervention, supportive psychotherapy, and medication, especially with drugs that quickly relieve distressing symptoms). Basing the diagnosis on these symptoms can be problematic when the individual has advanced disease and the illness itself is undermining functioning. It is also important to distinguish between fatigue and depression, which are often interrelated. The different mechanisms that give rise to these conditions can be treated separately.[1] In more advanced illness, focusing on despair, guilty thoughts, and a total lack of enjoyment of life is helpful in diagnosing depression. (Refer to the PDQ summary on Normal Adjustment and the Adjustment Disorders for further information.)

References

1. Jacobsen PB, Donovan KA, Weitzner MA: Distinguishing fatigue and depression in patients with cancer. Semin Clin Neuropsychiatry 8 (4): 229-40, 2003.  [PUBMED Abstract]
   
   
2. De Leeuw JR, De Graeff A, Ros WJ, et al.: Negative and positive influences of social support on depression in patients with head and neck cancer: a prospective study. Psychooncology 9 (1): 20-8, 2000 Jan-Feb.  [PUBMED Abstract]
   
   
3. Capuron L, Ravaud A, Neveu PJ, et al.: Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 7 (5): 468-73, 2002.  [PUBMED Abstract]
   
   
4. de Leeuw JR, de Graeff A, Ros WJ, et al.: Prediction of depression 6 months to 3 years after treatment of head and neck cancer. Head Neck 23 (10): 892-8, 2001.  [PUBMED Abstract]
   
   
5. Paice JA: Managing psychological conditions in palliative care. Am J Nurs 102 (11): 36-42; quiz 43, 2002.  [PUBMED Abstract]
   
   
6. Akechi T, Okuyama T, Sugawara Y, et al.: Major depression, adjustment disorders, and post-traumatic stress disorder in terminally ill cancer patients: associated and predictive factors. J Clin Oncol 22 (10): 1957-65, 2004.  [PUBMED Abstract]
   
   
7. Passik SD, Kirsh KL, Theobald D, et al.: Use of a depression screening tool and a fluoxetine-based algorithm to improve the recognition and treatment of depression in cancer patients. A demonstration project. J Pain Symptom Manage 24 (3): 318-27, 2002.  [PUBMED Abstract]
   
   
8. Loberiza FR Jr, Rizzo JD, Bredeson CN, et al.: Association of depressive syndrome and early deaths among patients after stem-cell transplantation for malignant diseases. J Clin Oncol 20 (8): 2118-26, 2002.  [PUBMED Abstract]
   
   
9. Nordin K, Glimelius B: Predicting delayed anxiety and depression in patients with gastrointestinal cancer. Br J Cancer 79 (3-4): 525-9, 1999.  [PUBMED Abstract]
   
   
10. Karnell LH, Funk GF, Christensen AJ, et al.: Persistent posttreatment depressive symptoms in patients with head and neck cancer. Head Neck 28 (5): 453-61, 2006.  [PUBMED Abstract]
    
    
11. Ciaramella A, Poli P: Assessment of depression among cancer patients: the role of pain, cancer type and treatment. Psychooncology 10 (2): 156-65, 2001 Mar-Apr.  [PUBMED Abstract]
    
    
12. Green AI, Austin CP: Psychopathology of pancreatic cancer. A psychobiologic probe. Psychosomatics 34 (3): 208-21, 1993 May-Jun.  [PUBMED Abstract]
    
    
13. Kugaya A, Akechi T, Okuyama T, et al.: Prevalence, predictive factors, and screening for psychologic distress in patients with newly diagnosed head and neck cancer. Cancer 88 (12): 2817-23, 2000.  [PUBMED Abstract]
    
    
14. Capuron L, Ravaud A, Gualde N, et al.: Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Psychoneuroendocrinology 26 (8): 797-808, 2001.  [PUBMED Abstract]
    
    
15. Capuron L, Ravaud A, Dantzer R: Early depressive symptoms in cancer patients receiving interleukin 2 and/or interferon alfa-2b therapy. J Clin Oncol 18 (10): 2143-51, 2000.  [PUBMED Abstract]
    
    
16. Green BL, Krupnick JL, Rowland JH, et al.: Trauma history as a predictor of psychologic symptoms in women with breast cancer. J Clin Oncol 18 (5): 1084-93, 2000.  [PUBMED Abstract]
    
    
17. Burgess CC, Ramirez AJ, Richards MA, et al.: Does the method of detection of breast cancer affect subsequent psychiatric morbidity? Eur J Cancer 38 (12): 1622-5, 2002.  [PUBMED Abstract]
    
    
18. Passik SD, Dugan W, McDonald MV, et al.: Oncologists' recognition of depression in their patients with cancer. J Clin Oncol 16 (4): 1594-600, 1998.  [PUBMED Abstract]
    
    
19. Chochinov HM, Wilson KG, Enns M, et al.: "Are you depressed?" Screening for depression in the terminally ill. Am J Psychiatry 154 (5): 674-6, 1997.  [PUBMED Abstract]
    
    
20. Akizuki N, Akechi T, Nakanishi T, et al.: Development of a brief screening interview for adjustment disorders and major depression in patients with cancer. Cancer 97 (10): 2605-13, 2003.  [PUBMED Abstract]
    
    
21. Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 67 (6): 361-70, 1983.  [PUBMED Abstract]
    
    
22. Morasso G, Costantini M, Baracco G, et al.: Assessing psychological distress in cancer patients: validation of a self-administered questionnaire. Oncology 53 (4): 295-302, 1996 Jul-Aug.  [PUBMED Abstract]
    
    
23. Lloyd-Williams M, Riddleston H: The stability of depression scores in patients who are receiving palliative care. J Pain Symptom Manage 24 (6): 593-7, 2002.  [PUBMED Abstract]
    
    
24. Love AW, Kissane DW, Bloch S, et al.: Diagnostic efficiency of the Hospital Anxiety and Depression Scale in women with early stage breast cancer. Aust N Z J Psychiatry 36 (2): 246-50, 2002.  [PUBMED Abstract]
    
    
25. Lloyd-Williams M, Friedman T, Rudd N: An analysis of the validity of the Hospital Anxiety and Depression scale as a screening tool in patients with advanced metastatic cancer. J Pain Symptom Manage 22 (6): 990-6, 2001.  [PUBMED Abstract]
    
    
26. Lloyd-Williams M, Spiller J, Ward J: Which depression screening tools should be used in palliative care? Palliat Med 17 (1): 40-3, 2003.  [PUBMED Abstract]
    
    
27. Roth AJ, Kornblith AB, Batel-Copel L, et al.: Rapid screening for psychologic distress in men with prostate carcinoma: a pilot study. Cancer 82 (10): 1904-8, 1998.  [PUBMED Abstract]
    
    
28. Derogatis LR, Melisaratos N: The Brief Symptom Inventory: an introductory report. Psychol Med 13 (3): 595-605, 1983.  [PUBMED Abstract]
    
    
29. Dugan W, McDonald MV, Passik SD, et al.: Use of the Zung Self-Rating Depression Scale in cancer patients: feasibility as a screening tool. Psychooncology 7 (6): 483-93, 1998 Nov-Dec.  [PUBMED Abstract]
    
    
30. Hegel MT, Moore CP, Collins ED, et al.: Distress, psychiatric syndromes, and impairment of function in women with newly diagnosed breast cancer. Cancer 107 (12): 2924-31, 2006.  [PUBMED Abstract]
    
    
31. Akizuki N, Yamawaki S, Akechi T, et al.: Development of an Impact Thermometer for use in combination with the Distress Thermometer as a brief screening tool for adjustment disorders and/or major depression in cancer patients. J Pain Symptom Manage 29 (1): 91-9, 2005.  [PUBMED Abstract]
    
    
32. Meyer HA, Sinnott C, Seed PT: Depressive symptoms in advanced cancer. Part 1. Assessing depression: the Mood Evaluation Questionnaire. Palliat Med 17 (7): 596-603, 2003.  [PUBMED Abstract]
    
    
33. Lynch ME: The assessment and prevalence of affective disorders in advanced cancer. J Palliat Care 11 (1): 10-8, 1995 Spring.  [PUBMED Abstract]
    
    
34. Lees N, Lloyd-Williams M: Assessing depression in palliative care patients using the visual analogue scale: a pilot study. Eur J Cancer Care (Engl) 8 (4): 220-3, 1999.  [PUBMED Abstract]
    
    
35. Patrick DL, Ferketich SL, Frame PS, et al.: National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002. J Natl Cancer Inst 95 (15): 1110-7, 2003.  [PUBMED Abstract]
    
    
36. Wellisch DK, Lindberg NM: A psychological profile of depressed and nondepressed women at high risk for breast cancer. Psychosomatics 42 (4): 330-6, 2001 Jul-Aug.  [PUBMED Abstract]
    
    
37. Roth AJ, Holland JC: Psychiatric complications in cancer patients. In: Brain MC, Carbone PP, eds.: Current Therapy in Hematology-Oncology. 5th ed. St. Louis, Mo: Mosby-Year Book, Inc., 1995, pp 609-18. 
    
    
38. Breitbart W, Holland JC: Psychiatric complications of cancer. Current Therapy in Hematology-Oncology 3: 268-74, 1988. 
    
    
39. Cancer chemotherapy. Med Lett Drugs Ther 29 (736): 29-36, 1987.  [PUBMED Abstract]
    
    
40. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther 33 (840): 21-8, 1991.  [PUBMED Abstract]
    
    
41. Drugs that cause psychiatric symptoms. Med Lett Drugs Ther 31 (808): 113-8, 1989.  [PUBMED Abstract]
    
    
42. Menzies H, Chochinov HM, Breitbart W: Cytokines, cancer and depression: connecting the dots. J Support Oncol 3 (1): 55-7, 2005 Jan-Feb.  [PUBMED Abstract]
    
    
43. Reuter K, Raugust S, Bengel J, et al.: Depressive symptom patterns and their consequences for diagnosis of affective disorders in cancer patients. Support Care Cancer 12 (12): 864-70, 2004.  [PUBMED Abstract]
    
    
44. Detmar SB, Aaronson NK, Wever LD, et al.: How are you feeling? Who wants to know? Patients' and oncologists' preferences for discussing health-related quality-of-life issues. J Clin Oncol 18 (18): 3295-301, 2000.  [PUBMED Abstract]
    
    
45. Nordin K, Wasteson E, Hoffman K, et al.: Discrepancies between attainment and importance of life values and anxiety and depression in gastrointestinal cancer patients and their spouses. Psychooncology 10 (6): 479-89, 2001 Nov-Dec.  [PUBMED Abstract]
    
    

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Intervention

Whether to initiate therapy for depression depends on the probability that the patient will recover spontaneously in the next 2 to 4 weeks, the degree of functional impairment, and the severity and duration of the depressive symptoms.[1] Studies have shown that treatment of major depression is optimized by a combination of pharmacotherapy and psychotherapy. Thus, even if a primary care physician or oncologist undertakes the treatment of depressive symptoms pharmacologically, a referral for psychotherapy or supportive counseling should be considered.

Individuals should be referred for a psychiatric consultation for the following reasons:

• A primary care physician or oncologist does not feel competent treating the patient for depression because of specific clinical features in the presentation (i.e., if prominent suicidal tendencies are present).



• The depressive symptoms treated by the primary physician are resistant to pharmacologic interventions after 2 to 4 weeks of intervention.



• The depressive symptoms are worsening rather than improving.



• Initiating treatment with antidepressant drugs, titrating drug doses, or continuing treatment is interrupted or made problematic by adverse effects attributable to the medication.



• The depressive symptoms are interfering with the patient's ability to be cooperative with medical treatment.[2-4]

There is a paucity of randomized, placebo-controlled trials assessing the risks and benefits of antidepressants in patients with cancer and depression or depressive symptoms. Furthermore, these studies are limited by methodological challenges and a lack of broad representation of children, adolescents, older adults, and minority groups.[5] In certain cases of depression in patients with cancer, antidepressant therapy may be indicated. A survey of prescribing patterns in outpatient oncology settings over a 2-year period found that antidepressants were prescribed for about 14% of patients.[6] In a systematic review of newer pharmacotherapies for depression in adults, the response rate for treatment of depression with antidepressants was found to be approximately 54%.[7] The efficacy of the newer pharmacotherapies is similar to that of older antidepressants for general medical patients, including older adults and those with coexisting medical or psychiatric illness.[7] The dropout rates due to adverse effects are approximately 11% for newer antidepressants and 16% for older antidepressants.[7] Because of the relative paucity of data regarding antidepressant use in oncology settings, there is considerable variability in practice patterns related to prescribing antidepressants in cancer patients. Although studies generally indicate that about 25% of all cancer patients are depressed, one study found that only 16% of cancer patients were receiving antidepressant medication.[8]

Antidepressant Studies

• In adults, a double-blind placebo-controlled trial comparing fluoxetine with desipramine in treating depressive symptoms in 40 women with cancer found both medications to be effective and well tolerated. There were greater improvements on several quality-of-life measures in patients who received fluoxetine.[9]



• One study compared paroxetine with amitriptyline in the management of depression in women with breast cancer. Both treatments were equally effective. Paroxetine was associated with significantly fewer anticholinergic adverse effects than amitriptyline.[10]



• In a randomized controlled trial comparing fluoxetine with a placebo, patients receiving fluoxetine were found to have improved quality of life and decreased depressive symptoms.[11] Using a symptom-based approach (similar to the management of other cancer-related symptoms such as pain or nausea), this study assessed for depression by use of a 2-item screening procedure focused on presence of anhedonia (little interest or pleasure in doing things) and depressed or hopeless mood. Most of the sample consisted of patients with mild-to-moderate levels of depressive symptoms regardless of whether they met the diagnostic criteria for depression. Generalization was enhanced by inclusion of a sample of mixed cancer types (e.g., breast, thoracic, genitourinary, gastrointestinal) from a predominantly community cancer care setting, an equal male/female ratio, and a relatively large sample size (n = 163). A subgroup of patients identified as having higher levels of depressive symptoms was most likely to benefit from the treatment.

Over the past few years, significant concerns have been raised about the risk of suicidal thinking and behavior with the use of antidepressants in children, adolescents, and young adults. Since 2003, U.S. and European regulators have issued several public health warnings on this topic. The first such advisory issued by the U.S. Food and Drug Administration (FDA) warned about a possible association between antidepressants and suicidal thinking and behavior in children and adolescents. In December 2003, the Medicines and Healthcare Products Regulatory Agency of the United Kingdom issued a letter to doctors advising against the use of antidepressants in anyone younger than 18 years.[12] In October 2004, the FDA mandated pharmaceutical companies to add a “black box” warning to the labeling of all antidepressants suggesting increased risk of suicidality in pediatric patients who were taking antidepressants. The FDA revised this black box warning in May 2007 to include young adults younger than 25 years.[13] The new, carefully worded warning emphasizes that the risk of suicidality is associated with both antidepressants and depression. In addition to raising concerns about increased sucidality in children, adolescents, and young adults, the warning acknowledges a significant protective effect of antidepressants in adults aged 65 and older. The meta-analysis that led to the initial black box warning in pediatric patients concluded that the antidepressants are associated with a twofold increase in suicidal ideation and behavior compared to the placebo in children and adolescents. A major meta-analysis published in the Journal of the American Medical Association reanalyzed the data from the child and adolescent studies (including seven studies not included in the initial meta-analysis), using a random-effects model. While this reanalysis found an overall increased risk of suicidal ideation/suicidal behavior consistent with the initial meta-analysis, the pooled risk differences were found to be smaller and statistically insignificant. Concerns have been raised that the unintended consequence of the warnings will be overly restricted use of antidepressants among those who benefit the most and, hence, an increase in suicidality that the warning seeks to prevent. A study examining U.S. and Dutch data suggests a drop in selective serotonin reuptake inhibitor (SSRI) prescriptions for children and adolescents since the black box warning was issued and a simultaneous increase in suicide rates in this patient population. In summary, the risk-benefit equation favors appropriate use of antidepressants with careful monitoring for suicidality. It is important to note that none of the studies that led to the black box warning included or focused on patients being treated for cancer. Clinical experience and results of small clinical trials suggest that antidepressants can be safely administered to adult cancer patients, although there are no large controlled clinical trials to support this position. When antidepressants are prescribed for patients with cancer, a careful monitoring plan should be implemented by individuals with expertise, and consultation referral should be made for patients who do not respond as anticipated or who present other concerns.

Most antidepressant prescribing is directed at the treatment of an existing depressive disorder or significant depressive symptoms. One study, however, supports the use of antidepressants to prevent depression in patients receiving high-dose interferon for adjuvant therapy of malignant melanoma.[14] The rationale for this approach is that treatment with high-dose interferon is associated with a particularly high rate of depression in this patient population, and proinflammatory cytokines implicated in the biological changes that result in depression may be directly reduced by antidepressants. In this double-blind study of patients receiving high-dose interferon, 2 of 18 patients in the paroxetine group developed depression during the first 12 weeks of therapy, compared with 9 of 20 patients in the placebo group (relative risk [RR] = 0.24; 95% confidence interval [CI], 0.08–0.93). Moreover, there were significantly fewer treatment discontinuations in the paroxetine group (5% vs. 35%, RR = 0.14; 95% CI, 0.05–0.85). Further study is required to confirm these findings and to determine whether prophylactic use of antidepressants has benefit in other treatment settings.

The choice of antidepressant depends on a patient's medical history and concomitant medical problems, the symptoms referable to depression, previous responses to antidepressant medications, and the side effects associated with the agents available.

The types of medications used to treat depression in patients with cancer include the SSRIs, tricyclic antidepressants (TCAs), and analeptic or CNS stimulant agents (i.e., amphetamines). The following table outlines the commonly used antidepressants and highlights starting dosages used in cancer patients. The Side Effects/Comments column identifies drug-specific side effects that may be clinically advantageous or problematic depending on the clinical situation when selecting antidepressant medications and monitoring patients receiving these drugs. Generally, there is a long latency period (3–6 weeks) from initiation of antidepressant medications until the onset of a therapeutic response. In many cases, antidepressant treatment begins at low doses followed by a period of gradual dose titration to achieve an optimum individualized response. Initial low doses may help to avoid initial side effects, but dose escalation may be required in order to see therapeutic effects. For some agents, there is a therapeutic window during which plasma concentrations correlate with a patient's antidepressant response (e.g., nortriptyline). For patients receiving these agents, serial drug concentration monitoring guides therapy and facilitates providing an adequate therapeutic trial, because plasma concentrations less than and greater than the defined therapeutic ranges are associated with treatment failure, suboptimal responses, and in the case of high drug concentrations, unnecessary toxicity.

When selecting an antidepressant drug, it is worthwhile to consider that side effects may have a clinical advantage. For example, some TCAs, such as amitriptyline, and atypical antidepressants, such as mirtazapine and trazodone, produce sedation and may be useful for agitated patients and for those who have difficulty getting to sleep. Consequently, treatment is often initiated as a single daily dose administered at bedtime. Although most patients will develop tolerance to antidepressants' sedative effects with continued treatment, the need for soporific agents may diminish with improvement in depressive symptoms.

When selecting antidepressants, either singly or in combination, consider the following:

• Target specific distressing symptoms.



• Evaluate coexistent medical problems that may be exacerbated by particular antidepressants.



• Minimize side effects and avoid worsening of current health status.



• Determine the patient's ability to swallow solid dosage forms; he or she may be able to take an antidepressant in liquid form (e.g., amitriptyline, nortriptyline, doxepin, fluoxetine). Alternatively, some antidepressants are available as parenteral dosage forms (e.g., amitriptyline and imipramine injection).



• Evaluate the patient's medication profile for potential interactions with antidepressant drugs.

The postulated mechanism of action of SSRIs involves the blockade of serotonin neuronal reuptake, leading to desensitization of serotonergic feedback receptors. All currently available SSRIs are equally efficacious; they differ primarily in their safety, tolerability, half-lives, and drug-drug interactions. While some side effects are more common with some SSRIs than with others, side effects and tolerability may differ significantly in individual patients. SSRIs have become the first-line treatment for depressive disorders, owing to their better tolerability side effect profile, especially in comparison with the TCAs. As discussed earlier, antidepressant studies conducted in patients with cancer are done mostly with SSRIs or TCAs. None of the clinical trials have included or focused on children and adolescents being treated for cancer.[16-19] Overall, the evidence on the efficacy of SSRIs for treating cancer-related depression remains limited, and more studies are needed to address the efficacy, safety, tolerability, and drug-drug interaction issues in the context of cancer and cancer treatments. The British Committee on Safety of Medicines considered only one of the SSRIs (fluoxetine) to have a favorable balance of risks and benefits, but it is only considered beneficial in approximately one in ten patients.[20] Consistent with this finding, age-stratified analyses of the child and adolescent studies found that for children younger than 12 years with major depression, only fluoxetine showed benefit over placebo.[21] As noted, none of the children or adolescents in these studies had cancer, so there are no reports available that address whether there are additional increased risks of adverse events associated with the use of SSRIs following exposure to different chemotherapeutic agents and/or central nervous system (CNS) radiation treatment. Frontline, alternative, effective, behavioral, and pharmacologic treatments for depression should be used for children and adolescents being treated for cancer. However, if the risks of depression are significant and SSRIs are considered, consultation from a child psychiatrist or neurologist is essential, and close monitoring of potential adverse events is crucial. No warning has been issued for adult use of SSRIs.

The optimal duration of antidepressant therapy for patients treated for depressive symptoms (without a depressive disorder) is unknown. Patients with a depressive disorder who achieve a beneficial response to antidepressant pharmacotherapy should continue treatment for a minimum of 4 to 6 months after depression resolves. When patients are discontinuing antidepressant medications, TCA doses should be tapered by approximately 25% per week to avoid cholinergic rebound (e.g., hypersalivation, diarrhea). In patients who experience intolerable adverse effects, however, doses may be tapered quickly. With the exception of fluoxetine, gradual tapering is advised when decreasing doses or discontinuing treatment for all SSRIs. Other antidepressants with short half-lives, such as venlafaxine, also should be tapered gradually. Withdrawal symptoms, both somatic and psychological, frequently emerge after abrupt discontinuation, during intermittent noncompliance, and sometimes during dose reduction; though these symptoms are generally mild, short-lived, and self-limiting, they can be distressing and may lead to missed workdays and decreased productivity. Mild symptoms can often be treated by reassuring a patient that they are usually transient. For more severe symptoms, it may be necessary to reinstate the dosage of the original antidepressant and slow the rate of taper. Symptoms of discontinuation may be mistaken for physical illness or relapse into depression and misdiagnosis may lead to unnecessary, costly tests and treatment. Thus, health care professionals need to be educated about the potential adverse effects of SSRI discontinuation.[22]

TCAs can produce abnormal myocardial conduction; thus, a cardiac history and a recent EKG should be obtained in patients with a history of cardiac problems. Many tricyclic antidepressants have a sedating effect; therefore, treatment typically is started at low doses at bedtime. The main exception is desipramine, which some patients find mildly stimulating and can be administered in the morning to reduce insomnia, if it develops. Daily doses are increased slowly every few days or at weekly intervals until symptoms improve. Many patients become tolerant to the drugs' sedative effects, and total daily doses may be divided and given during patients' waking cycles.

TCAs are still regarded as first-line agents for severe, major depression; however, SSRI use is increasing for that indication because of the effectiveness of SSRIs and the low risk of clinically significant side effects that are associated with TCAs, such as cardiac arrhythmias, hypotension, and anticholinergic effects. In addition, TCAs are highly toxic on overdose. Side effects commonly associated with the SSRIs include nausea, vomiting, diarrhea, somnolence, insomnia, headache, confusion, dizziness, asthenia, and sexual dysfunction. Drug-specific adverse effects associated with fluoxetine include gastric distress, brief periods of anxiety or agitation, and anorgasmia in females. Treatment with sertraline is sometimes complicated by dyspepsia, tremor, and ejaculatory delay in men.

The pharmacokinetic profiles of SSRIs permit them to be given once a day, thus improving patient compliance.[23] Sertraline and paroxetine have a half-life of approximately 20 hours; thus, steady-state systemic concentrations can be achieved within 1 week after starting treatment and altering dosage or administration schedules. In comparison, repeated dosing appears to inhibit fluoxetine metabolism; consequently, both fluoxetine and its active metabolite, norfluoxetine, may be present in the body for weeks after discontinuing treatment.

Clinicians who prescribe and monitor patients receiving antidepressants should also become familiar with their potential for interactions with other medications.[24] The SSRIs venlafaxine, nefazodone, and mirtazapine are metabolized by cytochrome P450 enzymes; their pharmacokinetics may be altered, or they may affect the clearance of drugs metabolized by the same enzymes. Marked differences exist, however, between the SSRIs and SSRI metabolites with regard to their effects on specific cytochrome P450 enzymes.[15] For example, both fluoxetine and norfluoxetine inhibit CYP3A4 isoenzyme; however, the metabolite is more potent than fluoxetine and in view of its longer half-life the potential for interactions may persist for weeks after fluoxetine is discontinued.[25] Understanding the similarities and differences in their pharmacology can aid clinicians in using these agents optimally and avoiding clinically important pharmacokinetic drug-drug interactions. In addition, since all SSRIs are highly protein-bound to albumin (± alpha-1 acid glycoprotein), clinicians must consider their potential for interactions with other highly protein-bound medications. Sertraline and paroxetine may be preferred in patients with renal or hepatic dysfunction since they are metabolized and excreted as inactive compounds.[26]

• Bupropion

  Bupropion is a unique alternative to tricyclics and SSRIs for treating persons with depression and cancer, especially when depression is accompanied by fatigue. Pharmacologically, bupropion is a weak inhibitor of monoamine reuptake and demonstrates a slight preference for dopamine transport inhibition; however, it may be metabolically converted to active substances with amphetamine-like activity that affect both dopamine and norepinephrine reuptake. Bupropion generally does not cause sexual dysfunction; therefore, it may be useful in treating patients who wish to remain sexually active and those who have experienced sexual dysfunction with other antidepressants. Bupropion treatment is initiated with doses of 75 mg once daily, preferably in the early part of the day. Patients may initially require a moderate- to long-acting sedative/hypnotic drug at bedtime for the insomnia, agitation, and motor restlessness sometimes associated with bupropion. Risk of seizure with bupropion may be as much as 4 times greater than is associated with other antidepressants. Single doses should not exceed 150 mg, a dose increase should not be greater than 100 mg of bupropion per day, and dose increases should be gradual—at least 3 days after a previous increase in dose. Because the risk of seizure markedly increases in patients receiving bupropion at doses between 450 mg and 650 mg, the total daily dose should not exceed 450 mg. Bupropion is contraindicated in patients with malignant diseases involving the brain and with a history of cranial trauma or seizure disorder [27] and in persons with a history of bulimia.[28]




• Venlafaxine

  Venlafaxine affects both norepinephrine and serotonin reuptake and enhances serotonin neurotransmission.[29] Venlafaxine does not produce the same uncomfortable antimuscarinic and antiadrenergic side effects as the TCAs; however, it does produce side effects similar to the SSRIs, particularly nausea, headache, somnolence, and dry mouth. In some patients, venlafaxine may cause sustained increases in blood pressure; blood pressure should therefore be evaluated before treatment is started, monitored after treatment is initiated, and monitored after doses are increased. Venlafaxine is given twice a day, with food.




• Trazodone and nefazodone

  The primary actions of the atypical antidepressants trazodone and nefazodone are not well established. Although they both antagonize serotonin reuptake, they are many times weaker in this respect compared with SSRIs. Trazodone is active, and both agents are metabolized to compounds that have agonistic activity at some serotonin receptors (5-HT₁). Both agents may have additional active metabolites that contribute to their clinical activity.[29] Nefazodone is reported to be useful in patients with agitated depression and may be better tolerated than the SSRIs. Nefazodone can complicate some patients' management because it is a potent inhibitor of hepatic cytochrome P450 3A4 isoenzymes. Its use is, therefore, relatively contraindicated in patients who are receiving methadone and absolutely contraindicated in those receiving terfenadine or astemizole.




• Mirtazapine

  There is growing clinical experience with mirtazapine in persons with cancer. Pharmacologically, mirtazapine is a noradrenergic and specific serotonergic antidepressant. It competitively antagonizes presynaptic alpha-adrenergic receptors (alpha2) and serotonin receptors (5-HT₂ and 5-HT₃), the net result of which enhances norepinephrine release and noradrenergic neurotransmission.[29,30] Sedation is the predominating side effect at subtherapeutic low doses (<15 mg/day), and anecdotal evidence suggests that sedation decreases at higher doses. Its side-effect profile also includes increased appetite, which may cause weight gain, dizziness, dry mouth, and constipation.[31] Although it is a structural analog of mianserin (an antidepressant that is marketed in Europe), mirtazapine has rarely been implicated in producing severe blood dyscrasias, including agranulocytosis, as has mianserin.[32] Little is known about mirtazapine interactions with other drugs, but it is thought to have a lesser risk of clinically significant drug interactions than SSRIs.[33] The initial dose for mirtazapine is 15 mg per day given at bedtime. Doses may be increased at intervals not less than 1 to 2 weeks, up to a maximum daily dose of 45 mg.

Benzodiazepines can be used to effectively treat the anxiety that may be associated with depression. In patients receiving antidepressant medications and benzodiazepines concomitantly, the latter drugs may be discontinued after patients' depressive symptoms begin to abate; however, both agents can be continued safely if needed. Benzodiazepines should never be stopped abruptly because withdrawal symptoms with possible seizures may occur. The dose of benzodiazepines should be tapered slowly at a rate of approximately 25% every 3 to 4 days.

Clinical experience suggests that analeptic agents (e.g., methylphenidate and dextroamphetamine) are useful at low doses for patients whose symptoms include depressed mood, apathy, decreased energy, poor concentration, and weakness.[34] They are particularly useful for patients with advanced cancer who have a limited life expectancy (weeks to a few months). Compared with traditional antidepressants such as the TCAs and SSRIs that take 3 to 4 weeks to take effect, the psychostimulants often demonstrate antidepressant effects within a few days of starting treatment. They promote a sense of well-being, decreased fatigue, and increased appetite. Analeptic agents can be helpful in countering the sedating effects of opioids, and in comparison with antidepressants, they are rapidly effective. Adverse effects associated with analeptic agents include insomnia, euphoria, and mood lability. High doses and long-term use may produce anorexia, nightmares, insomnia, euphoria, or paranoia.

Methylphenidate and dextroamphetamine are administered in divided doses early in a patient's waking cycle to avoid sleep disturbances, e.g., insomnia and nighttime arousal. Like benzodiazepines, these medications are adjuncts to antidepressant medications; they may be started concomitant with an antidepressant and discontinued when depressive symptoms abate.[35,36]

The use of monoamine oxidase inhibitors (MAOIs) in the cancer population has been limited because the nutritional requirements of a tyramine-free diet are generally more difficult to accomplish in patients receiving antineoplastic treatments. MAOIs are contraindicated in patients receiving opioids, sympathomimetics, and procarbazine because of the potential for developing hypertensive crisis.

MAOIs may cause adverse reactions when taken with other medications and certain foods. MAOIs impair the metabolism of morphine and other opioids as well as barbiturates and may lead to exaggerated ventilatory depression. Meperidine HCl (Demerol), an opioid, has been associated with hypertension, hyperpyrexia, skeletal muscle rigidity, seizures, and coma when used with MAOIs.[42] Exaggerated effects of antihistamines, anticholinergics, and tricyclic antidepressants may be secondary to impaired metabolism by MAOIs. In addition, the hypoglycemic effects of insulin and oral sulfonylureas may be potentiated by MAOIs.

MAOIs may also interact with specific anesthetic drugs used during surgery.[43] Cancer patients in particular may frequently undergo surgical procedures and should alert their anesthesiologist of all medications. Postoperative pain should not be treated with meperidine HCl. MAOIs should neither be taken with procarbazine, a chemotherapeutic agent used in the treatment of lymphomas and brain tumors, nor used with other antidepressants.

The U.S. Food and Drug Administration (FDA) has recently approved a transdermal antidepressant that may have particular value in the treatment of the depressed cancer patient who is unable to swallow or take medications by mouth. The antidepressant selegiline (sold under the trade name EMSAM) is an irreversible MAOI. To date, the drug has not been evaluated for the treatment of depression in cancer patients.

Many of the usual dietary restrictions (low-tyramine diet) and drug-drug interactions (the product should not be used with meperidine, propoxyphone, or methadone) are germane to selegiline (see table below). However, according to the package insert, the 20-mg skin patch (which delivers 6 mg of selegiline in a 24-hour period) can be used without the dietary restrictions found on all MAOIs marketed to date. This recommendation is supported by clinical trials and other evidence submitted to the FDA. The two higher doses (a 30-mg patch that delivers 9 mg in 24 hours and a 40-mg patch that delivers 12 mg in 24 hours) carry the usual dietary warning. This drug has not been evaluated in cancer patients for safety and efficacy.

Selegiline is a nonselective MAOI, inhibiting not only the MAO-B enzyme in the central nervous system but also MAO-A elsewhere in the body. In the digestive tract, MAO-A normally metabolizes tyramine, a dietary amine that is found in high concentrations in foods such as aged cheese and red wine. The breakdown of tyramine in the gut prevents significant amounts of it from being absorbed and circulated throughout the body. Tyramine is a potent pressor—leading to constriction of blood vessels—which ultimately results in increased blood pressure. Large amounts of tyramine can lead to hypertensive crises, resulting in stroke, heart attack, and even death. Because the medication is absorbed from the skin patch and bypasses the gut wall, it is thought that transdermal selegiline will have a significantly reduced effect on MAO-A in the digestive tract. In addition, at lower doses, selegiline is thought to inhibit MAO-B preferentially, while at higher doses both A and B isoenzymes are affected. With significantly reduced inhibition of digestive tract MAO-A, dietary restrictions are not considered necessary for the lower dose. In considering starting this drug, consult with a pharmacist about multiple classes of drug-drug interactions. This drug has not been evaluated in people with cancer.[45]

Foods that contain large amounts of tyramine, such as cheese, chicken liver, chocolate, beer, and wine, may provoke hypertension (initially manifesting as headache) and cardiac dysrhythmias.

There has been much interest in the use of St. John's wort (SJW, Hypericum perforatum) as an herbal antidepressant. Its use has become widely advertised as an over-the-counter supplement for mood enhancement.

In the United States, dietary supplements are regulated as foods, not drugs. Premarket approval by the FDA is not required unless specific disease prevention or treatment claims are made, which is often not the case with SJW. Because a review for manufacturing consistency is not required for dietary supplements and no specific standards for dose or purity exist, there may be considerable variation from lot to lot for all products marketed as dietary supplements, including SJW.

Promotional statements about SJW may address mood enhancement and positive outlook. It may be found as a stand-alone supplement or in combination with other herbs, vitamin and mineral supplements, or food products such as teas. The FDA issued a warning highlighting the results from a study conducted by the National Institutes of Health that showed a significant drug interaction between SJW and indinavir, a protease inhibitor used to treat HIV infection. In this study, concomitant administration of SJW and indinavir substantially decreased indinavir plasma concentrations, potentially due to induction of the cytochrome P450 metabolic pathway.[46]

While its specific mechanisms of action are unclear, there are 3 presumed active compounds in the herb. One of these compounds is a mild MAOI (see above precautions). Historically, prescription MAOIs have been used to treat depression as well as Parkinson disease, narcolepsy, and occasionally hypertension, but they are rarely used today. The side effects of SJW include dry mouth, dizziness, gastrointestinal (GI) distress, fatigue, and confusion.

A randomized double-blind placebo-controlled trial involving 200 adult outpatients with major depressive disorder compared the safety and efficacy of SJW with placebo. This study was designed to address the numerous methodological flaws in the existing literature [47] that served as the basis for the meta-analysis that had concluded that SJW is significantly superior to placebo.[48] This study represents the first report of a large-scale randomized placebo-controlled trial of SJW in the United States. This study does not support significant antidepressant or antianxiety effects of SJW. Specifically, compared with placebo, there were no significant differences in response rates in the overall sample of outpatients with major depression. On the basis of these trial data indicating lack of efficacy in depressed patients in primary care settings, as well as the lack of properly designed positive trials in cancer patients, SJW should not be recommended for major depression in cancer patients.

The following tables highlight tips that may be useful in determining what medication is best to use for a particular patient. The tables focus on the effects these medications may have beyond their antidepressant effects that may decrease or increase patient distress, such as fatigue, insomnia, and nausea and vomiting.

It should be noted that electroconvulsive therapy (ECT) is a useful and safe therapy when other interventions have not succeeded in relieving the depressive syndrome that may represent a life-threatening complication of treatable cancer.[49,50] Experience is limited, however, in using ECT in patients receiving mirtazapine and trazodone, and there are no clinical studies establishing the use of ECT in patients receiving SSRIs. Prolonged seizures have occurred rarely in patients receiving fluoxetine.

Traditionally, depressive symptomatology was managed with insight-oriented psychotherapy, which is quite useful for some people with cancer. For many other people, these symptoms are best managed with some combination of crisis intervention, brief supportive psychotherapy, and cognitive-behavioral techniques.

Psychotherapy for depression has been offered in a variety of forms. Most interventions have been time limited (ranging between 4 and 30 hours), have been offered in both individual and small-group formats, and have included a structured educational component about cancer or a specific relaxation component.[51]

Cognitive-behavioral psychotherapy has been one of the most prominent types of therapies studied in recent investigations. Cognitive-behavioral interventions focus on altering specific coping strategies aimed at improving overall adjustment and typically focus on specific thoughts and their relationship to emotions and behaviors. Understanding and altering one’s thoughts can change emotional reactions and accompanying behaviors. For example, frequent, intrusive, uncontrollable thoughts about loss, life changes, or death can cause poor concentration and precipitate feelings of sadness, guilt, and worthlessness. In turn, these feelings can result in increased sleep, withdrawal, and isolation. A cognitive-behavioral intervention focuses on the intrusive thoughts, often challenging their accuracy or rationality and noting specific patterns of cognitive distortions. Simultaneously, patients develop specific cognitive coping strategies that are designed to alter emotional reactions and accompanying behaviors. The end result is improved coping, enhanced adjustment, and better overall quality of life.

Other goals of psychotherapy include enhancing coping skills, directly reducing distress, improving problem-solving skills, mobilizing support, reshaping negative or self-defeating thoughts, and developing a close personal bond with a knowledgeable, empathic health care provider.[52-56] Consultation with a cleric or a member of a pastoral care department may also help some individuals.

Specific goals of these therapies include the following:

• Assist people with cancer and their families by answering questions about the illness and its treatment, clarifying information, correcting misunderstandings, giving reassurance, and normalizing responses to the illness and its effect on their families. Explore the present situation with the patient and how it relates to his or her previous experiences with cancer.



• Assist with problem solving, bolster the patient’s usual adaptive defenses, and help the patient and family develop further supportive and adaptive coping mechanisms. Identify maladaptive coping mechanisms and assist the family in developing alternative coping strategies. Explore areas of related stressors (e.g., family role and lifestyle changes), and encourage family members to support and share concerns with each other.



• When the focus of treatment changes from cure to palliation, reinforce strongly that, though curative treatment has ended, the team will aggressively treat symptoms as part of the palliation plan; the patient and family will not be abandoned; and staff members will work very hard to maintain comfort, control pain, and maintain the dignity of the patient and his or her family members.

Cancer support groups can be useful adjunctive therapies in the treatment of cancer patients.[57,58] Recent support group interventions have demonstrated significant effects on mood disturbance, use of positive coping strategies, improvement in quality of life, and positive immune responses.[59-61] Support groups can be found through The Wellness Community, the American Cancer Society, and many other community resources, including the social work departments of medical centers or hospitals.

Psychotherapy as a treatment for depression in the general adult mental health population has been extensively researched and found to be effective.[62] Recent reviews have also concluded that psychotherapy is an effective intervention for cancer patients experiencing depression.[63,51] In studies designed to prevent the occurrence of depression (i.e., patients not selected because of their depressive symptoms), intervention effects are positive, though small to moderate effect sizes have been reported (effect sizes range from 0.19 to 0.54).[51] However, in those studies in which patients were intentionally selected because they exhibited depressive symptoms, intervention effects were strong (effect size, 0.94).[63] An effect size of 0.94 indicates that the average patient in the treatment group was advantaged, compared with approximately 82% of patients in the control group.

One well-designed randomized clinical trial of a cognitive-behavioral intervention for depressed cancer patients investigated the effect of training in problem solving on symptoms of depression.[64] The intervention consisted of 10 1.5-hour weekly individual psychotherapy sessions focused on training to become an effective problem solver. Problem-solving tasks were emphasized, including skills in (a) better defining and formulating the nature of problems, (b) generating a wide range of alternative solutions, (c) systematically evaluating consequences of a solution while deciding on an optimal one, and (d) evaluating outcome after solution implementation. Between-session homework with tasks relevant to each step was assigned, and patients were provided with a written manual and encouraged to refer to it as problems arose. One hundred thirty-two adult cancer patients were randomly assigned to the problem-solving treatment or a wait-list control. Overall results showed both improved problem-solving abilities and clinically significant decreases in symptoms of depression.

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16. Emslie GJ, Rush AJ, Weinberg WA, et al.: A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 54 (11): 1031-7, 1997.  [PUBMED Abstract]
    
    
17. Emslie GJ, Heiligenstein JH, Wagner KD, et al.: Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry 41 (10): 1205-15, 2002.  [PUBMED Abstract]
    
    
18. Keller MB, Ryan ND, Strober M, et al.: Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 40 (7): 762-72, 2001.  [PUBMED Abstract]
    
    
19. Wagner KD, Ambrosini P, Rynn M, et al.: Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 290 (8): 1033-41, 2003.  [PUBMED Abstract]
    
    
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33. Owen JR, Nemeroff CB: New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine. Depress Anxiety 7 (Suppl 1): 24-32, 1998.  [PUBMED Abstract]
    
    
34. Homsi J, Nelson KA, Sarhill N, et al.: A phase II study of methylphenidate for depression in advanced cancer. Am J Hosp Palliat Care 18 (6): 403-7, 2001 Nov-Dec.  [PUBMED Abstract]
    
    
35. Feighner JP, Boyer WF: Perspectives in Psychiatry. Volume 1. Selective Serotonin Re-uptake Inhibitors: The Clinical Use of Citalopram, Fluoxetine, Fluvoxamine, Paroxetine, and Sertraline. New York, NY: John Wiley & Sons Ltd, 1991. 
    
    
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37. Meyers CA, Weitzner MA, Valentine AD, et al.: Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol 16 (7): 2522-7, 1998.  [PUBMED Abstract]
    
    
38. Olin J, Masand P: Psychostimulants for depression in hospitalized cancer patients. Psychosomatics 37 (1): 57-62, 1996 Jan-Feb.  [PUBMED Abstract]
    
    
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Suicide Risk in Cancer Patients

Demographics and Statistics

Studies indicate that the incidence of suicide in cancer patients can be equal to the incidence in the general population or up to 2 to 10 times as frequent. Some studies suggest that while relatively few cancer patients commit suicide, they are at increased risk for suicide.[1-3] One population-based study utilizing data from the Cancer Registry of Norway linked to the Register of Deaths at Statistics Norway indicated an increased relative risk of suicide in the decade 1990-1999 within 2 years of diagnosis for males and females; however, the relative risk for females was nonsignificant. For both sexes, the risk was highest in the first months after diagnosis, and there was a significant decrease in relative risk over decades.[4] Passive suicidal thoughts are relatively common among cancer patients. The relationships between suicidal tendency and the desire for hastened death, requests for physician-assisted suicide, and/or euthanasia are complex and poorly understood.[5] Men with cancer are clearly at an increased risk of suicide compared with the general population, with a relative risk as high as 2.3.[1,2] Overdosing with analgesics and sedatives is the most common method of suicide among persons with cancer,[1,2] with most cancer-related suicides occurring at home. Reports identify a higher incidence of suicide in patients with oral, pharyngeal, and lung cancers and in HIV-positive patients with Kaposi sarcoma.[1,2,5] The actual incidence of suicide in cancer patients is probably underestimated. There may be reluctance to report death by suicide in these circumstances.[6]

Risk factors for suicide in the cancer population are as follows:

General Risk Factors

• History of psychiatric disorders, especially those associated with impulsive behavior (e.g., borderline personality disorders).
• Family history of suicide.
• History of previous/prior suicide attempts.
• Depression.
• Substance abuse.
• Recent death of a friend or spouse.
• Few social supports.

Cancer-Specific Risk Factors

• Oral, pharyngeal, and lung cancers (often associated with heavy alcohol and tobacco use).
• Advanced stage of disease and poor prognosis.
• Confusion/delirium.
• Inadequately controlled pain.
• Presence of deficit symptoms (e.g., loss of mobility, loss of bowel and bladder control, amputation, sensory loss, paraplegia, inability to eat and to swallow, exhaustion, fatigue).

References

1. Bolund C: Suicide and cancer: I. Demographic and social characteristics of cancer patients who committed suicide in Sweden, 1973-1976. Journal of Psychosocial Oncology 3 (1): 17-30, 1985. 
   
   
2. Bolund C: Suicide and cancer: II. Medical and care factors in suicides by cancer patients in Sweden, 1973-1976. Journal of Psychosocial Oncology 3 (1): 31-52, 1985. 
   
   
3. Fox BH, Stanek EJ 3rd, Boyd SC, et al.: Suicide rates among cancer patients in Connecticut. J Chronic Dis 35 (2): 89-100, 1982.  [PUBMED Abstract]
   
   
4. Hem E, Loge JH, Haldorsen T, et al.: Suicide risk in cancer patients from 1960 to 1999. J Clin Oncol 22 (20): 4209-16, 2004.  [PUBMED Abstract]
   
   
5. Breitbart W, Krivo S: Suicide. In: Holland JC, Breitbart W, Jacobsen PB, et al., eds.: Psycho-oncology. New York, NY: Oxford University Press, 1998, pp 541-7. 
   
   
6. Holland JC: Psychologic aspects of cancer. In: Holland JF, Frie E, eds.: Cancer Medicine. 2nd ed. Philadelphia, Pa: Lea & Febiger, 1978, pp 1175-1203. 
   
   

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Assessment, Evaluation, and Management of Suicidal Patients

Assessment

Patients who are suicidal require careful assessment. In the assessment of suicide, it is important to recognize that the risk of suicide increases if the patient reports ideation (i.e., thoughts of suicide) plus a plan (i.e., description of the means). Risk continues to increase to the extent that the plan is lethal. Lethality is determined by an assessment of how likely death would follow, if the reported plan were carried out. Factors to consider in assessing lethality include availability of the means, reversibility of the means (once begun can it be stopped), and proximity to help. In the cancer patient reporting suicidal ideation, it is essential to determine whether the underlying cause is a depressive illness or an expression of the desire to have ultimate control over intolerable symptoms.[1] Prompt identification and treatment of major depression is essential in lowering the risk for suicide in cancer patients. Risk factors, particularly hopelessness (which is an even stronger predictive factor for suicide than is depression) should be carefully assessed.[2] The assessment of hopelessness is not straightforward in the patient with advanced disease with no hope of cure. It is important to assess the underlying reasons for hopelessness, which may be related to poor symptom management, fears of painful death, or feelings of abandonment.[3] Of 220 Japanese patients who had cancer and who were diagnosed with major depression after being referred for psychiatric consultation, approximately 50% reported suicidal ideation. In a retrospective analysis of predictors of suicidal ideation, researchers found that those with more symptoms of major depression and poorer physical functioning were significantly more likely to report suicidal ideation.[4]

Establishing rapport is of prime importance in working with suicidal cancer patients as it serves as the foundation for other interventions. The clinician must believe that talking about suicide will not cause the patient to attempt suicide. On the contrary, talking about suicide legitimizes this concern and permits patients to describe their feelings and fears, providing a sense of control.[5] A supportive therapeutic relationship should be maintained, which conveys the attitude that much can be done to alleviate emotional and physical pain. (Refer to the PDQ summary on Pain for more information.) A crisis intervention-oriented psychotherapeutic approach should be initiated that mobilizes as much of a patient's support system as possible. Contributing symptoms (e.g., pain) should be aggressively controlled and depression, psychosis, agitation, and underlying causes of delirium should be treated.[5] (Refer to the PDQ summary on Cognitive Disorders and Delirium for more information.) These problems are most frequently managed in the medical hospital or at home. Although uncommon, psychiatric hospitalization can be helpful when there is a clear indication and the patient is medically stable.[5]

In clinical practice, the goal of management of suicidal patients is to attempt to prevent suicide that is driven by desperation due to poorly controlled symptoms. Prolonged suffering due to poorly controlled symptoms can lead to such desperation. Thus, effective symptom management is critical to decrease psychological distress in suicidal cancer patients.[5] Patients close to the end of life may be unable to maintain a wakeful state without high levels of emotional or physical pain. This frequently leads to suicidal thoughts or requests for aid in dying. Such patients may require sedation to ease their distress. In practice, the number of such patients is extremely variable. Reports on sedating treatments at the end of life highlight a confusing terminology of descriptors and perceived problems.[7,8] In addition, the range for patients sedated at the end of life varies from 3% to 52%. The issue of sedation in terminally ill patients is controversial, but it is becoming a more accepted practice, particularly in the hospice setting.[3]

At times, it may be important to limit access to potentially lethal medications for patients considered at risk for suicide. When potentially lethal medications are limited, it is important to weigh the impact on symptom management against the impact on suicide risk because poorly controlled symptoms may contribute to risk. Furthermore, suicidal patients will often have other means available to complete suicide attempts and these must also be evaluated. Strategies to lessen suicidal risk include frequent contact to reassess suicidal risk and symptom control, as well as regular delivery of limited quantities of medications facilitating rapid dose titration for effective management of poorly controlled symptoms when necessary. For patients receiving parenteral or intrathecal opioids, programmable pumps with limited access to programming and locked, inaccessible cartridges may provide an element of safety.

Strategies to lessen suicide risk in cancer patients include the following:

• Use medications that work rapidly to alleviate distress (e.g., a benzodiazepine for anxiety or a stimulant for fatigue) while waiting for the clinical effects from antidepressant therapy.



• Pay scrupulous attention to symptom management.



• Limit access as appropriate to quantities of medications that are lethal in overdose.



• Maintain frequent contact with and closely observe the patient.



• Avoid having the patient spend long periods of time alone.



• Mobilize support for the patient.



• Carefully assess the patient's psychological responses at each crisis point over the course of the disease.

When suicide complicates bereavement, the loss can be especially difficult for survivors. A pattern of reactions that includes feelings of abandonment, rejection, anger, relief, guilt, responsibility, denial, identification, and shame may occur. This pattern is modified by such factors as the nature and intensity of the relationship, the nature of the suicide, the deceased person's age and physical condition, the perceived support network, and the survivor's coping skills and cultural/religious background.[5] Assisting survivors through the bereavement period is important. Mutual support groups are helpful in reducing isolation, providing opportunities for venting feelings, and finding ways to cope with the aftermath of suicide. (Refer to the PDQ summary on Loss, Grief, and Bereavement for further information.)

Staff reactions to the suicide of a patient are similar to those seen in family members, although staff often do not feel that they have the same right to express their feelings. The suicide of a patient may lead a staff member to question his or her professional judgment. It is often helpful for the staff to conduct a psychological autopsy in an attempt to understand why and how the suicide happened, signs and symptoms of risk, and how routines might be altered to prevent similar problems in the future.[5]

The principle of respecting and promoting patient autonomy has been one of the driving forces behind the hospice movement and right-to-die issues that range from honoring living wills to promoting euthanasia. These issues can create a conflict between patient autonomy and the physician's obligation to beneficence.[9]

Answers to the questions of euthanasia and physician-assisted suicide belong to the realm of the law, ethics, medicine, and philosophy. Physicians and other health care professionals have essential clinical roles to play in addressing and untangling these issues when working with depressed, terminally ill patients.[1,10-15] Additionally, religious and cultural issues may strongly influence this decision-making process. A 1994 survey suggests that hospice physicians favor vigorous pain control and strongly approve of the right of patients to refuse life support even if life is secondarily shortened. However, these physicians strongly oppose euthanasia or assisted suicide, clearly making a sharp distinction between these 2 interventions.[9] Often patients who specifically request physician-assisted suicide can be prescribed measures that augment their comfort, relieve symptoms, and obviate considering drastic measures.[1] A recent study suggests that agreement with euthanasia is associated with male sex, lack of religious beliefs, and general beliefs about the suffering of cancer patients.[16] A 1995 study of persons with advanced cancer who expressed a consistent and strong desire for hastened deaths suggested that this desire is related to the presence of depression. Patients with the desire to die should be carefully assessed and treated for depression as necessary. Whether their desire to die would persist or decrease with improvement in mood disorder has not yet been studied.[17] It is important to maintain a shared decision-making process from the beginning of the professional relationship.[18] (Refer to the PDQ summary on Last Days of Life for more information.)

References

1. Massie MJ, Gagnon P, Holland JC: Depression and suicide in patients with cancer. J Pain Symptom Manage 9 (5): 325-40, 1994.  [PUBMED Abstract]
   
   
2. Kovacs M, Beck AT, Weissman A: Hopelessness: an indicator of suicidal risk. Suicide 5 (2): 98-103, 1975 Summer.  [PUBMED Abstract]
   
   
3. Breitbart W, Passik SD: Psychiatric aspects of palliative care. In: Doyle D, Hanks GW, MacDonald N, eds.: Oxford Text Book of Palliative Medicine. New York: Oxford University Press, 1993, pp 609-26. 
   
   
4. Akechi T, Okamura H, Yamawaki S, et al.: Why do some cancer patients with depression desire an early death and others do not? Psychosomatics 42 (2): 141-5, 2001 Mar-Apr.  [PUBMED Abstract]
   
   
5. Breitbart W, Krivo S: Suicide. In: Holland JC, Breitbart W, Jacobsen PB, et al., eds.: Psycho-oncology. New York, NY: Oxford University Press, 1998, pp 541-7. 
   
   
6. Roth AJ, Holland JC: Psychiatric complications in cancer patients. In: Brain MC, Carbone PP, eds.: Current Therapy in Hematology-Oncology. 5th ed. St. Louis, Mo: Mosby-Year Book, Inc., 1995, pp 609-18. 
   
   
7. Fainsinger RL: Use of sedation by a hospital palliative care support team. J Palliat Care 14 (1): 51-4, 1998 Spring.  [PUBMED Abstract]
   
   
8. Fainsinger RL, Landman W, Hoskings M, et al.: Sedation for uncontrolled symptoms in a South African hospice. J Pain Symptom Manage 16 (3): 145-52, 1998.  [PUBMED Abstract]
   
   
9. Miller RJ: Supporting a cancer patient's decision to limit therapy. Semin Oncol 21 (6): 787-91, 1994.  [PUBMED Abstract]
   
   
10. Masdeu JC: Physician-assisted suicide and euthanasia. JAMA 276 (3): 196-7, 1996.  [PUBMED Abstract]
    
    
11. Siegler M: Is there a role for physician-assisted suicide in cancer? No. Important Adv Oncol : 281-91, 1996.  [PUBMED Abstract]
    
    
12. Back AL, Wallace JI, Starks HE, et al.: Physician-assisted suicide and euthanasia in Washington State. Patient requests and physician responses. JAMA 275 (12): 919-25, 1996.  [PUBMED Abstract]
    
    
13. Marzuk PM: Suicide and terminal illness. Death Stud 18 (5): 497-512, 1994. 
    
    
14. Suarez-Almazor ME, Belzile M, Bruera E: Euthanasia and physician-assisted suicide: a comparative survey of physicians, terminally ill cancer patients, and the general population. J Clin Oncol 15 (2): 418-27, 1997.  [PUBMED Abstract]
    
    
15. Howard OM, Fairclough DL, Daniels ER, et al.: Physician desire for euthanasia and assisted suicide: would physicians practice what they preach? J Clin Oncol 15 (2): 428-32, 1997.  [PUBMED Abstract]
    
    
16. Suarez-Almazor ME, Newman C, Hanson J, et al.: Attitudes of terminally ill cancer patients about euthanasia and assisted suicide: predominance of psychosocial determinants and beliefs over symptom distress and subsequent survival. J Clin Oncol 20 (8): 2134-41, 2002.  [PUBMED Abstract]
    
    
17. Chochinov HM, Wilson KG, Enns M, et al.: Desire for death in the terminally ill. Am J Psychiatry 152 (8): 1185-91, 1995.  [PUBMED Abstract]
    
    
18. Chandler SW, Trissel LA, Weinstein SM: Combined administration of opioids with selected drugs to manage pain and other cancer symptoms: initial safety screening for compatibility. J Pain Symptom Manage 12 (3): 168-71, 1996.  [PUBMED Abstract]
    
    

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Pediatric Considerations for Depression

There is limited information concerning the incidence of depression in healthy children. One study of children seen in a general practice showed that 38% had problems that required major intervention by a psychiatrist. Another study of children aged 7 to 12 years showed a 1.9% incidence of depression. If applied to the general population of the United States, these results show that 40,000 12-year-olds are depressed. Teachers have estimated that as many as 10% to 15% of their students are depressed. The Joint Commission on Mental Health of Children states that 1.4 million children younger than 18 years need immediate help for disorders such as depression; only one third of these children receive help for their disorder.[1]

Most children cope with the emotional upheaval related to cancer and demonstrate not only evidence of adaptation but positive psychosocial growth and development. A minority of children, however, develops psychological problems including depression, anxiety, sleep disturbances, difficulties in interpersonal relationships, and noncompliance with treatment. These children require referral and intervention by a mental health specialist.[2]

In one of the first studies of depression in childhood cancer, 114 children and adolescents were studied, and 59% were found to have mild psychiatric problems.[3] A study of 17 adolescent and 21 pediatric oncology patients, all of whom were administered a self-report psychosocial life events inventory, showed that the adolescent samples had a mean level of depressive symptoms similar to that of the general population. The pediatric oncology sample demonstrated significantly lower depressive symptoms than the general population.[4] Forty-one adolescent survivors of childhood cancer were assessed using questionnaires and interviews to determine the psychosocial status of the survivors; most survivors were functioning well, and depression was rare.[5] A study of long-term cancer survivors and their mothers, comparing the survivors with a group of 92 healthy children, showed that the majority of former patients were functioning within normal limits. Not surprisingly, children with severe late effects had more depressive symptoms.[6] One researcher looked at the characteristics of psychiatric consultations in a pediatric cancer center and found that adjustment disorder was the chief psychosocial diagnosis. This finding is similar to results obtained from adult cancer patients. This study also found that anxiety reactions were more common in the younger pediatric patients and depressive disorders were more common in older patients.[7] In a study conducted in 1988 with a sample of 30 adolescent cancer patients, the rate of major depression was not greater than the rate for the population at large.[8] One review reported a 17% incidence of depression using the Diagnostic and Statistical Manual for Mental Disorders, 3rd Edition criteria.[9]

Most cancer survivors demonstrate general resiliency and successful psychological adjustment to the disease and its treatment. Despite evidence for successful adaptation, most studies document psychological difficulties in a significant subset of cancer survivors.

The term depression refers to a symptom, a syndrome, a set of psychological responses, or to an illness.[1] Duration and intensity of the behavioral manifestation (e.g., sadness) differentiates the symptoms from the disorder. For example, a sad affect can be a child's response to trauma and is usually of short duration; however, a depressive illness is characterized by long duration, and is associated with insomnia, irritability, changes in eating habits, and severe impairment of the child's scholastic and social adjustment. Depression should be considered whenever any behavior problem persists. Depression does not refer to transitory moments of sadness, but rather to a disorder that affects development and interferes with realization of the child's innate potential.[1]

Some manifestations of depression in a school-aged child include anorexia, lethargy, sad affect, aggression, weeping, hyperactivity, somatization, fear of death, frustration, feelings of sadness or hopelessness, self criticism, frequent day dreaming, low self-esteem, school refusal, learning problems, slow movements, vacillating hostility towards parents and teachers, and loss of interest in previously pleasurable activities. Differentiating these symptoms from behavioral responses to normal developmental stages is important.[1]

Assessment of depression includes determination of the child's family situation, level of emotional maturity, ability to cope with illness and treatment, age, state of development, previous experience with illness, and personal ego strength.[10]

A comprehensive assessment for childhood depression is the basis for accurate diagnosis and treatment. Evaluation of the child and family situation focuses on the pediatric health history, behaviors observed by the practitioner or reported by others (e.g., parents, teachers), interviews with the child, and judicial use of tests such as the Beck Depression Inventory or the Child Behavior Checklist.[10]

In discussing the diagnosis of childhood depression, experts stress the importance of understanding childhood depression as an entity distinct from depression in adults. This is due to the fact that developmental issues in childhood are distinctly different from those of adulthood.[11]

A model of childhood affective disorders uses the following explicit criteria:[12]

• Dysphoric mood (children younger than 6 years must also have a sad facial expression).
• At least 4 of the following signs or symptoms present every day for a period of at least 2 weeks:
  • Appetite disturbance.
  • Insomnia or hypersomnia.
  • Psychomotor agitation or retardation.
  • Loss of interest or pleasure in usual activities (children younger than 6 years must also have signs of apathy).
  • Fatigue or loss of energy.
  • Feelings of worthlessness, self-reproach, or excessive, inappropriate guilt.
  • Diminished ability to think or concentrate.
  • Recurrent thoughts of death or suicide.

Treatment regimens implemented in childhood depression reflect theoretical models, etiology, and manifestations of the disorder.[1] Individual and group psychotherapy are commonly utilized as the primary treatment modality and are directed at helping the child to master his or her difficulties and to enable the child to develop in an optimal manner. Play therapy may be used as a means of exploring a younger child's view of himself or herself, the disease, and its treatment. The child needs to be helped from the beginning to explore and understand, at a level appropriate for his or her developmental age, the diagnosis of cancer and the treatments involved.[1]

As is the case with depression in adult cancer patients, there are few, if any, revealing trials of antidepressants in children with cancer. One author described rapid clinical response to low doses (<2 mg/kg/day) of imipramine or amitriptyline for 8 depressed children with cancer.[13] Another author described the use of benzodiazepines such as lorazepam, diazepam, alprazolam, and clonazepam for the treatment of anxiety disorders. Trials of benzodiazepines should be short term. These drugs should be tapered slowly when they are discontinued.[14]

The combined use of tricyclic antidepressants and neuroleptics in the management of 3 children with severe symptoms of depression and anxiety has been reported. The children studied were in the terminal phases of their disease and were treated with a combination of low-dose amitriptyline and haloperidol. Levels of anxiety and depression were decreased, and this intervention allowed the patients and their families to deal with issues involved in death and dying.[15]

Significant concern about the potential for suicide as a side effect of selective serotonin reuptake inhibitors (SSRIs) has led the U.S. Food and Drug Administration (FDA) to issue a caution about their use that includes the importance of careful monitoring of potential risks.[16] Before this FDA Health Advisory was issued, clinical experience and the results of small clinical trials suggested that antidepressants can be safely administered to adult cancer patients, although there are no controlled clinical trials to support this position. The risk/benefit ratio for use of SSRIs may not be as favorable for children and adolescents. Several multicenter, double-blind, randomized, placebo-controlled clinical trials using SSRIs with children and adolescents with major depressive disorder but not cancer found modest improvements for fluoxetine,[17,18] paroxetine,[19] and sertraline.[20] Balancing these improvements were reports of serious adverse events that included worsening of psychiatric symptoms, increased suicidal ideation and gestures, increased conduct problems or hostility with paroxetine,[19] and suicide and suicide attempts with sertraline.[20] None of these clinical trials have included or focused on children and adolescents being treated for cancer. Risk/benefit concerns have reached the level of international regulatory concern. The Medicines and Healthcare Products Regulatory Agency of Great Britain has recommended that most of the drugs in the SSRI category not be used with children and adolescents,[21] and the FDA raised similar concerns in a Talk Paper and subsequently issued a “black box” warning.[16] A major meta-analysis published in the Journal of the American Medical Association reanalyzed the data from the child and adolescent studies [22] (including seven studies not included in the initial meta-analysis [23]) using a random-effects model. While this reanalysis found an overall increased risk of suicidal ideation/suicide attempt consistent with the initial meta-analysis, the pooled risk differences were found to be smaller and statistically insignificant.[22] Furthermore, another study examining the U.S. and Dutch data suggests a drop in SSRI prescriptions for children and adolescents and a simultaneous increase in suicide rates in this patient population since the FDA Health Advisory was issued.[24] In summary, the risk-benefit equation favors appropriate use of antidepressants with careful monitoring for suicidality.[25] The British Committee on Safety of Medicines considered only one of the SSRIs (fluoxetine) to have a favorable balance of risks and benefits, but it is only considered beneficial in approximately one in ten patients.[26] Consistent with this finding, age-stratified analyses of the child and adolescent studies found that for children younger than 12 years with major depression, only fluoxetine showed benefit over placebo.[22] As noted, none of the children or adolescents in these studies had cancer, so there are no reports available that address whether there are additional increased risks of adverse events associated with the use of SSRIs following exposure to different chemotherapeutic agents and/or central nervous system radiation treatment. Frontline, alternative, effective, behavioral, and pharmacologic treatments for depression should be used for children and adolescents being treated for cancer. However, if the risks of depression are significant and SSRIs are considered, consultation from a child psychiatrist or neurologist is essential, and close monitoring of potential adverse events is crucial.

Refer to the PDQ summary on Pediatric Supportive Care for more information.

References

1. Deuber CM: Depression in the school-aged child: implications for primary care. Nurse Pract 7 (8): 26-30, 68, 1982.  [PUBMED Abstract]
   
   
2. Kazak AE: Psychological issues in childhood cancer survivors. J Assoc Pediatr Oncol Nurses 6 (1): 15-6, 1989.  [PUBMED Abstract]
   
   
3. O'Malley JE, Koocher G, Foster D, et al.: Psychiatric sequelae of surviving childhood cancer. Am J Orthopsychiatry 49 (4): 608-16, 1979.  [PUBMED Abstract]
   
   
4. Kaplan SL, Busner J, Weinhold C, et al.: Depressive symptoms in children and adolescents with cancer: a longitudinal study. J Am Acad Child Adolesc Psychiatry 26 (5): 782-7, 1987.  [PUBMED Abstract]
   
   
5. Fritz GK, Williams JR, Amylon M: After treatment ends: psychosocial sequelae in pediatric cancer survivors. Am J Orthopsychiatry 58 (4): 552-61, 1988.  [PUBMED Abstract]
   
   
6. Greenberg HS, Kazak AE, Meadows AT: Psychologic functioning in 8- to 16-year-old cancer survivors and their parents. J Pediatr 114 (3): 488-93, 1989.  [PUBMED Abstract]
   
   
7. Rait DS, Jacobsen PB, Lederberg MS, et al.: Characteristics of psychiatric consultations in a pediatric cancer center. Am J Psychiatry 145 (3): 363-4, 1988.  [PUBMED Abstract]
   
   
8. Tebbi CK, Bromberg C, Mallon JC: Self-reported depression in adolescent cancer patients. Am J Pediatr Hematol Oncol 10 (3): 185-90, 1988 Fall.  [PUBMED Abstract]
   
   
9. Kashani J, Hakami N: Depression in children and adolescents with malignancy. Can J Psychiatry 27 (6): 474-7, 1982.  [PUBMED Abstract]
   
   
10. Archenbach TM, ed.: Manual for the Child Behavior Checklist and Revised Child Behavior Profile. Burlington, Vt: T.M. Achenbach, 1983. 
    
    
11. American Psychiatric Association.: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR. 4th rev. ed. Washington, DC: American Psychiatric Association, 2000. 
    
    
12. Malmquist CP: Major depression in childhood: why don't we know more? Am J Orthopsychiatry 53 (2): 262-8, 1983. 
    
    
13. Pfefferbaum-Levine B, Kumor K, Cangir A, et al.: Tricyclic antidepressants for children with cancer. Am J Psychiatry 140 (8): 1074-6, 1983.  [PUBMED Abstract]
    
    
14. Coffey BJ: Review and update: benzodiazepines in childhood and adolescence. Psychiatr Ann 23 (6): 332-9, 1993. 
    
    
15. Maisami M, Sohmer BH, Coyle JT: Combined use of tricyclic antidepressants and neuroleptics in the management of terminally ill children: a report on three cases. J Am Acad Child Psychiatry 24 (4): 487-9, 1985.  [PUBMED Abstract]
    
    
16. U.S. Food and Drug Administration.: Antidepressant Use in Children, Adolescents, and Adults. Rockville, Md: Food and Drug Administration, Center for Drug Evaluation and Research, 2007. Available online. Last accessed July 8, 2008. 
    
    
17. Emslie GJ, Rush AJ, Weinberg WA, et al.: A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 54 (11): 1031-7, 1997.  [PUBMED Abstract]
    
    
18. Emslie GJ, Heiligenstein JH, Wagner KD, et al.: Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry 41 (10): 1205-15, 2002.  [PUBMED Abstract]
    
    
19. Keller MB, Ryan ND, Strober M, et al.: Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 40 (7): 762-72, 2001.  [PUBMED Abstract]
    
    
20. Wagner KD, Ambrosini P, Rynn M, et al.: Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 290 (8): 1033-41, 2003.  [PUBMED Abstract]
    
    
21. Safety Review of Antidepressants Used by Children Completed. London, UK: Medicines and Healthcare Products Regulatory Agency, 2003. Available online. Last accessed July 7, 2008. 
    
    
22. Bridge JA, Iyengar S, Salary CB, et al.: Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA 297 (15): 1683-96, 2007.  [PUBMED Abstract]
    
    
23. Hammad TA, Laughren T, Racoosin J: Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 63 (3): 332-9, 2006.  [PUBMED Abstract]
    
    
24. Gibbons RD, Brown CH, Hur K, et al.: Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry 164 (9): 1356-63, 2007.  [PUBMED Abstract]
    
    
25. Leon AC: The revised black box warning for antidepressants sets a public health experiment in motion. J Clin Psychiatry 68 (7): 1139-41, 2007.  [PUBMED Abstract]
    
    
26. Ramchandani P: Treatment of major depressive disorder in children and adolescents. BMJ 328 (7430): 3-4, 2004.  [PUBMED Abstract]
    
    

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Pediatric Considerations for Suicidality

Adolescents with cancer tend to fight to live rather than succumb to death, either natural death or suicide. Suicide in the absence of a major mental disorder is as rare among adolescents as it is for adults.[1] Refusal of treatment by adolescents has not been found to be a means of attempting suicide. Rather, noncompliance is associated with the belief that life and death are determined by fate, luck, or God. The adolescent believes that his or her disease is outside of the realm of control and is in the hands of God or some other force.

In the general pediatric population, about 2,000 adolescents in the United States die by suicide each year. Suicide consistently ranks as the second or third leading cause of death for persons between the ages of 15 and 34 years. One author suggests that before puberty, children are less vulnerable to suicide because of their cognitive immaturity, which makes planning and implementing a lethal attempt difficult. Even accounting for underreporting, it is evident that the youth suicide rate has more than doubled during the period from 1956 to 1993. The increasing youth suicide rate has been attributed to the increase in and prevalence of adolescent alcohol abuse; chronic and acute illnesses were not described as major factors contributing to suicide.[1]

The suicide rate for male adolescents is 4 times as high as the rate for females. The suicide rate for white adolescents is about twice as high as the rate for blacks and Hispanics. In one study, 53% of 380 high school students had thought about killing themselves, with 9% of this group having attempted suicide. In another study, a representative sample of 11,631 high school students reported that 27% of the students had seriously considered suicide, with 16% having a plan in mind, 8% having made an attempt, and 2% making attempts that required medical attention. The authors of this study extrapolated from these results that 276,000 high school students make suicide attempts requiring medical attention.[1] To date, little is known about the actual prevalence of suicidal thinking and suicide attempts in childhood cancer.

Because little is known about suicide risk factors specifically in childhood cancer, one could assess the risk factors for the general pediatric population with the following:[2]

1. Biologic factors include family history of psychiatric disorders such as depression, schizophrenia, alcoholism, drug dependence, and conduct disorder. Genetic predisposition to low levels of serotonin are associated with depression.



2. Predisposing life events include an early family history of parental abuse, negative life event such as loss of a parent, childhood bereavement, and disturbed, hostile interfamilial relationships. Many psychosocial factors and negative life events have not been found to cause subsequent suicidal behavior.



3. Psychosocial factors include the very nature of adolescence itself, with its concurrent desire to experiment with drugs and alcohol. Conflict or confusion about sexual orientation can be a factor in adolescent suicide. In addition, characteristics such as perfectionism, impulsivity, inhibition, and isolation all contribute to the likelihood of the adolescents having thoughts of suicide.



4. Psychiatric disorders are found in 95% of all completed suicides in adolescents. The following disorders are seen in most suicides: major depressive illness, schizophrenia, alcoholism, drug dependence, and conduct disorder. However, most individuals with psychiatric disturbances do not commit suicide.



5. Contagion is an expression that describes the phenomenon of young people identifying with the suicidal behavior of others. Those who are in a vulnerable state may imitate suicidal behavior. A completed suicide in a childhood cancer setting should lead to support and monitoring of the victim's peers.



6. The availability of lethal weapons such as a gun in the house can precipitate suicide.



7. Precipitating events such as a diagnosis of cancer can change a state of potential risk to actual suicide. In this instance there is usually:
   • A preexisting psychiatric disorder.
   
   
   
   • A number of current life stressors.
   
   
   
   • An upsetting event such as academic failure.
   
   
   
   • Life-threatening disease.
   
   
   

One author describes the hopelessness that may be felt by cancer survivors as being instrumental in acts of suicide. She asserts that when an adolescent cannot determine reasons to live, hopelessness occupies the thought process and suicide presents a reasonable solution.[3]

The management of suicide is carried out through the careful evaluation and assessment of a child with cancer and his or her family. The multiple factors that make life intolerable for some children need to be addressed. Suicide prevention must include:

• Individual assessment.



• Referral to appropriate health professionals.



• Appropriate drug management.



• Individual psychiatric therapy coupled with family therapy.

The evidence of continuity of childhood and adolescent depression and of familial transmission of this disorder from parent to child would seem to argue that the same agents used for adults would be effective in childhood. The efficacy of antidepressants in children and adolescents has not been established.[4]

Refer to the PDQ summary on Pediatric Supportive Care for more information.

References

1. Clark DC: Suicidal behavior in childhood and adolescence: recent studies and clinical implications. Psychiatr Ann 23 (5): 271-83, 1993. 
   
   
2. Callahan J: Blueprint for an adolescent suicidal crisis. Psychiatr Ann 23 (5): 263-70, 1993. 
   
   
3. Perrone J: Adolescents with cancer: are they at risk for suicide? Pediatr Nurs 19 (1): 22-5, 1993 Jan-Feb.  [PUBMED Abstract]
   
   
4. Ryan ND: The pharmacologic treatment of child and adolescent depression. Psychiatr Clin North Am 15 (1): 29-40, 1992.  [PUBMED Abstract]
   
   

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Changes to This Summary (10/24/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

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Additional PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment

  Treatment options for childhood cancers.

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• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)

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• PDQ® Cancer Information Summaries: Genetics

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• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine

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