February 2008, Volume 12, Number 1

Article

Putting Evidence Into Practice^®: Interventions for Depression

Caryl D. Fulcher, MSN, APRN, BC, Terry Badger, PhD, APRN, BC, FAAN, Ashley K. Gunter, BSN, RN, OCN^®, Joyce A. Marrs, MS, APRN, BC, AOCNP^®, and Jill M. Reese, BSN, RN, OCN^®

Depression and depressive symptoms are prevalent in people with cancer, yet interventions for depression are a low priority for most oncology care providers. Barriers to diagnosis and treatment include beliefs by patients and providers that depression is an expected correlate of cancer diagnosis, the reluctance of patients to share psychological concerns, and the reticence of some professionals to assess patients with cancer for depressive symptoms in the midst of busy oncology settings. Intervening to diminish depressive symptoms in people with cancer is important because depression has been associated with poorer quality of life, recovery, and possibly survival. This article reviews and summarizes the evidence for pharmacologic and nonpharmacologic interventions for people with cancer and depression and identifies opportunities for future research and practice change.

At a Glance

· Depression is a prevalent, comorbid condition for people with cancer, but barriers often prevent appropriate assessment and intervention.

· Evidence shows that psychoeducational and psychosocial interventions, particularly cognitive behavioral therapy, are beneficial in managing depressive symptoms in patients with various types of cancer.

· Complementary therapies are gaining popularity, but currently no sufficient, high-quality studies support the use of such therapies in people with cancer.

The Oncology Nursing Society (ONS) has led efforts to identify patient outcomes that are influenced by nursing interventions. Nursing interventions must be within the scope of nursing practice, integral to the processes of nursing care (Given & Sherwood, 2005), and selected based on research examining intervention effectiveness. The 2006 ONS Putting Evidence Into Practice^® (PEP) Depression Intervention Project Team reviewed, critiqued, and summarized the research evidence for nursing interventions related to depression in people with cancer. This article is an evidence-based review of pharmacologic and non-pharmacologic nursing interventions used to treat adult patients with cancer and depression.

Oncology care providers long have recognized that patients and their families experience emotional distress associated with cancer and its treatment. Emotional distress is an important problem in cancer survivorship because it significantly influences cancer recovery (Alferi, Carver, Antoni, Weiss, & Duran, 2001; Helgeson, Snyder, & Seltman, 2004; Manne et al., 2003; Osborne, Elsworth, & Hopper, 2003; Owen, Klapow, Roth, Nabell, & Tucker, 2004), quality of life (QOL) (Heiney et al., 2003; Vega et al., 2002; Vos, Garssen, Visser, Duivenvoorden, & de Haes, 2004), and possibly even long-term survival (Maunsell, Brisson, & Deschenes, 1995; Weihs, Enright, Simmens, & Reiss, 2000). Depression, the most common emotional distress experienced, is estimated to have prevalence from 1.5%–50% in breast cancer survivors (Massie, 2004; Trask, 2004; Zabora, BrintzenhofeSzoc, Curbow, Hooker, & Piantadosi, 2001), depending on how depression is defined.

Much has been written about depression, although the term’s many definitions may contribute to the lack of understanding of the seriousness of depressive symptoms and can provide barriers to its treatment. Styron (1990) wrote in Darkness Visible: A Memoir of Madness that it was “a noun with a bland tonality and lacking any magisterial presence, used indifferently to describe an economic decline or a rut in the ground, a true wimp of a word for such a major illness” (p. 37). Depression is defined for this review as the entire range of feelings and emotions expressed by individuals with cancer as they manage personal and illness-related problems; it includes normal sadness in response to loss as well as chronic, depressed emotional affect and clinical depression that meets specific criteria for a psychiatric disorder (Barsevick, Sweeney, Haney, & Chung 2002). Patients suffering with depressive symptoms that fail to meet the criteria for diagnosis or with sufficient symptoms to meet a diagnosis are at risk for poor health outcomes (Zabora et al., 2001).

One barrier to effective assessment and intervention for depression is the belief of many providers and patients that depression is a natural reaction to the diagnosis of cancer rather than a comorbid and serious condition (Passik et al., 1998). This myth limits identification of depression as a condition that can be treated. Another barrier is the reluctance of many patients to share their emotional symptoms with busy healthcare professionals; conversely, providers often are uncomfortable probing into patients’ psychological distress.

To overcome these barriers, standards and guidelines such as the National Comprehensive Cancer Network (NCCN) Standards of Care for Distress Management (NCCN, 2008) call for screening, evaluating, and treating depression in all patients with cancer (see Figure 1). Oncology nurses can play a significant role in (a) recognizing visual and verbal cues of anxiety and depression, (b) screening for depressive symptoms with the many valid screening tools available, and (c) integrating evidence-based interventions into their practice.

Descriptions of screening tools for depression can be found on the ONS Outcomes Resource Area (www.ons.org/outcomes/measures/summaries.shtml#dep). Oncology nurses can advocate for patients and their families to improve recognition and treatment of depressive symptoms and depression and collaborate with mental health professionals to ensure comprehensive care. Figure 2 provides signs and symptoms of depression.

The ONS PEP Depression Intervention Project Team explored the evidence on interventions to answer the question, “What can oncology nurses do to assist people with cancer who also have depressive symptoms or major depressive disorder?”

Methods

The workgroup searched MEDLINE^®, CINAHL^®, PubMed^®, and PsycINFO using the search terms interventions, psychosocial interventions, psychoeducational interventions, supportive counseling, and cancer and depressive symptoms or depression or major depressive disorder. Years searched were 2001–2006, and the search ended September 30, 2006. In some cases, earlier articles were reviewed in an attempt to comprehensively cover appropriate literature.

Articles were eliminated if they did not involve an intervention targeted for depressive symptoms or major depressive disorder, or if they were exclusively about caregivers or pediatric patients. A health services librarian was consulted to assist in the search.

Highlights of Reviewed Literature

Nine systematic reviews or meta-analyses from the identified time period found the highest evidence in support of psychosocial and psychoeducational interventions and pharmacologic interventions. The detailed ONS PEP card can be found in the Appendix. Each study and review was rated on strength of evidence as identified by the ONS Weight-of-Evidence Classification Schema (see Table 1). The system critically appraises evidence sources from strongest (multiple, well-designed, randomized, controlled trials with samples more than 100 subjects) to weakest (e.g., qualitative designs, case studies, opinions). From there, interventions were classified using a weight-of-evidence schema (Mitchell & Friese, n.d.), which ranged from Recommended for Practice for those with strong supportive evidence to Likely to be Effective, Benefits Balanced With Harms, Effectiveness not Established, Effectiveness Unlikely, or Not Recommended for Practice. Interventions reviewed are psychosocial and psychoeducational, pharmacologic, and complementary.

Psychoeducational and Psychosocial Interventions

Evidence at the highest level (Barsevick et al., 2002; Bennett & Badger, 2005; Given et al., 2004; Newell, Sanson-Fisher, & Savolainen, 2002; Osborne et al., 2003; Pirl, 2004; Uitter-
hoeve et al., 2004; Williams & Dale, 2006) supports the benefit of psychoeducational and psychosocial interventions in the management of depressive symptoms during and following cancer treatment in patients with different types of cancer. Psychoeducational and psychosocial interventions include cognitive-behavioral therapy, patient education and information, counseling and psychotherapy, behavioral therapy, and supportive interventions. Cognitive-behavioral therapy is defined as any specific psychological or psychosocial intervention that is relatively brief, goal oriented, based on learning principles of behavior change, and directed at effecting change in a specific clinical outcome (Osborn, Democada, & Feuerstein, 2006). It teaches problem-solving skills and challenges “black and white” thinking to help reframe attitudes. Counseling and psychotherapy refer to interactive verbal interventions, including nondirective, psychodynamic, existential, supportive, and crisis interventions; nurses who provide such interventions have advanced education and training. Of the interventions studied, the most evidence is for cognitive-behavioral therapy. Patient education, therapeutic social support, and information take many forms but clearly are important and essential actions for oncology nurses.

Barsevick et al. (2002) examined scientific studies, qualitative or quantitative systematic reviews, and practice guidelines published from 1980–2000, and concluded that psychoeducational interventions reduced depressive symptoms in patients with cancer. Behavior therapy or counseling alone or in combinations with cancer education was found to be beneficial. The same recommendations were made in a meta-analysis by Williams and Dale (2006), which also included pharmacologic interventions. Although considerable variability exists in frequency, duration, and type of psychosocial intervention, most studies support that the interventions are effective for reducing depressive symptoms; thus, they are recommended for practice. Although less evidence shows that psychosocial interventions are effective for treating those with depression, the ONS PEP Weight-of-Evidence Classification Schema indicates that enough evidence exists to recommend such interventions for practice.

Pharmacologic Interventions

Antidepressant Medications

Although much has been written about antidepressant use in patients with depression and cancer, few randomized, controlled trials have examined the effectiveness of antidepressants. Treatment studies of patients with cancer and depression support use of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), mianserin (atypical antidepressant not available in the United States), and others (Goodnick & Hernandez, 2000; Lan Ly, Chidgey, Addington-Hall, & Hotopf, 2002; Pirl, 2004; Schwartz, Lander, & Chochinov, 2002). Four reviews were identified that supported the benefits of antidepressant medication in patients with cancer (Pirl; Schwartz et al.), other comorbid medical illness (Goodnick & Hernandez), and palliative care (Lan Ly et al.). Studies measuring depression at less than five weeks showed less benefit, likely because the time to reach therapeutic effect may be four to eight weeks. No differences were found in effectiveness between TCAs and SSRIs; however, the lower incidence of side effects with SSRIs makes them preferable in patients with cancer. Although no studies have specifically examined the newer serotonin-norepinephrine reuptake inhibitor duloxetine in patients with depression and cancer, its similarity to venlafaxine makes it likely to be similarly effective.

Patients with malignant melanoma, traditionally treated with interferon alfa, are known to experience depression as a side effect of treatment. Musselman et al. (2001) prescribed paroxetine two weeks prior to the initiation of interferon alfa and continued it for the first 12 weeks of therapy in a double-blind study of 40 patients. Dosage ranged from 10–40 mg daily. Major depression developed in only 2 of the 18 patients in the paroxetine group compared to 9 of the 20 on placebo. Paroxetine treatment also significantly decreased the likelihood that interferon would have to be discontinued because of severe depression.

Clinical practice guidelines, another comprehensive, evidence-based tool to assist healthcare professionals in providing optimal care, support the benefit of medication interventions. The National Health and Medical Research Council, Australia (2003), which published Clinical Practice Guidelines for the Psychosocial Care of Adults With Cancer, concluded that the treatment of depression should incorporate psychotherapeutic and medication interventions. Although clear evidence supports the efficacy of antidepressant medication in treating depression in patients with cancer, no evidence exists that any particular antidepressant is superior to another. Antidepressant selection should be based on side-effect profiles and patient needs. For example, the sedating properties of the TCAs may be beneficial for some patients, and TCAs may potentiate opioid analgesia in those with pain. The long half-life of fluoxetine makes it less desirable in patients with hepatic or renal dysfunction; in such cases, another antidepressant is preferable (Health and Medical Research Council, Australia; National Cancer Institute, 2007). Other guidelines for the treatment of depression also provide useful information about medication management in the treatment of depression in adults (American Psychiatric Association, 2000; Ministry of Health, Singapore, 2004). Those guidelines contain information about selecting antidepressants, adjusting doses, assessing response, switching medications, managing the continuation and maintenance phases of antidepressant treatment, and discontinuing treatment. The guidelines are not specific to depression in patients with cancer. Although the guidelines document that depression can coexist with medical conditions, they are not specific for the physical impairments of many patients with cancer. In contrast, the National Comprehensive Cancer Network (2008) has published guidelines detailing algorithms describing care of patients with cancer and mood disorders or adjustment disorders with depressed mood. Pharmacology with antidepressants is an effective intervention and is recommended for practice.

Methylphenidate

One phase II study (Homsi et al., 2001) and one systematic review (Rozans, Dreisbach, Lertora, & Kahn, 2002) explored methylphenidate (Ritalin^®, Novartis) in patients with depression in advanced cancer (cancer sites studied included breast, esophagus, pancreas, colorectal, and other). The advantage of the central nervous system stimulant is its reported safety and rapid onset of action. It is used most often in advanced cancer and palliative situations, when doses typically are prescribed twice a day starting at 5 mg and titrated until a response is obtained or side effects dictate discontinuance. Giving the dose early in the day with food is recommended to increase absorption and decrease insomnia. Homsi et al. found that the maximum daily dose needed for resolution of depression was 20 mg. In the Rozans et al. systematic review of nine studies, methylphenidate was useful in treating depression in a variety of malignancies, with more than 80% of patients responding favorably and less than 20% reporting side effects. Methylphenidate also is used to address opioid-induced somnolence, augment opioid effects, improve cognitive functioning in patients with cancer, and decrease pain scores. Those benefits may contribute to mood improvement. Using the ONS PEP Weight-of-Evidence Classification Schema, the team concluded that methylphenidate is likely to be effective.

Complementary Interventions

Complementary and alternative therapies used to treat depression in patients with cancer are gaining popularity and prevalence. Unfortunately, few randomized, controlled studies of complementary interventions have been conducted in people with cancer and depression. Included in this category are massage therapy, relaxation therapy, hypnotherapy, and many others.

Massage Therapy

Massage is the manipulation of soft-tissue areas of the body, offered to assist in relaxation, aid in sleep, and relieve muscle tension and pain (Cassileth & Vickers, 2004). Studies examining the effect of massage therapy on depression are beginning to emerge, but effectiveness has not been established. The most consistent effect on symptom relief in patients with cancer was reduction in anxiety (Fellowes, Barnes, & Wilkinson, 2004). Some short-term reduction in depression has been demonstrated; self-report symptom scores of depression reduced by about 50% 2–48 hours after massage (Cassileth & Vickers), but more and better-quality studies are needed to recommend this intervention.

Relaxation Therapy

Relaxation therapy refers to techniques that focus on inducing a relaxed physical and mental state, such as progressive muscle relaxation with or without guided imagery, hypnosis, and autogenic training (Leubbert, Dahme, & Hasenbring, 2001; Sloman, 2002). Leubbert et al.’s meta-analysis evaluated 15 randomized, controlled studies conducted from 1980–1995. Relaxation training was found to have a significant impact on reducing cancer treatment–related side effects, including emotional adjustment variables (e.g., depression, anxiety, hostility). In a study of 56 people with advanced cancer, progressive muscle relaxation and guided imagery were taught to patients; a reduction in depression was found in all three treatment groups (Sloman). Findings from the review included a small but significant benefit on treatment-related side effects, including depression. According to the ONS PEP Weight-of-Evidence Classification Schema, relaxation as a method is likely to be effective in managing depressive symptoms.

Hypnotherapy

Hypnotherapy is a behavior therapy to induce heightened concentration, receptivity, and relaxation (Sadock & Sadock, 2003). Rajasekaran, Edmonds, and Higginson’s (2005) systematic review reported results of 27 studies prior to 2003. Terminally ill adult patients with cancer obtained relief from depression, anxiety, and pain, but only 1 of the 27 was a randomized, controlled study. Although few adverse effects were reported overall, reports were made of patients who were unable to enter a deep trance or who were frightened by the treatment (Rajasekaran et al.). Most studies were considered of poor quality with very small sample sizes. Therefore, according to the ONS PEP Weight-of-Evidence Classification Schema, effectiveness is not established for hypnotherapy in managing depression; further research is needed.

Other Complementary Interventions

St. John’s wort, an herb known to treat mild to moderate depression, should be avoided during chemotherapy or radiation or when surgery is planned because it can adversely impact the efficacy of some chemotherapeutic agents and prescription medications (Deng & Cassileth, 2005). Other complementary interventions such as nutritional and herbal supplements, yoga, acupuncture, aromatherapy, Healing Touch, exercise, and meditation have not been studied specifically in people with cancer, or insufficient studies have demonstrated effectiveness to recommend for practice (Pirl, 2004). Although some studies (Post-White et al., 2003; Sloman, 2002) show promising results and benefits of such methods to reduce mood disturbance, stress, pain, and other symptoms, effectiveness in decreasing depressive symptoms in patients with cancer has not been established; therefore, the method cannot be recommended.

Implications

The evidence documenting the ill effects of depression as a comorbid symptom or diagnosis supports the need for improved recognition and intervention. Oncology nurses are well positioned to assess for depression during the cancer treatment trajectory. A routine including questions about patient concerns, difficulties, hopes, and expectations with supportive responses and information leads to further education or referral. Nurses must educate themselves about depression as a symptom and an illness and can select one of many, well-established depression assessment tools to incorporate into their practices (see Table 2). In addition, each practice setting must develop methods to provide or make referrals for psychosocial, psychoeducational, and pharmacologic interventions. Oncology nurses with additional expertise may do so or can collaborate with other professionals to improve cancer care.

Conclusions

Depression, whether classified as depressive symptoms or diagnosis, is prevalent and distressing for many patients with cancer and their families. Depression can contribute to negative health outcomes, including increased morbidity and mortality (Manne et al., 2003; Osborne et al., 2003; Owen et al., 2004; Vega et al., 2002; Vos et al., 2004; Weihs et al., 2000). Although many of the interventions used to treat depression may be effective in patients with cancer and depression, patients with cancer are not offered the interventions routinely. Depression remains underdiagnosed and undertreated.

The strongest evidence exists for psychosocial and psychoeducational interventions. Further research is needed to examine intervention dosage (frequency and duration) and combinations of psychosocial interventions and medications with diverse cancer populations. Pharmacologic interventions also have been found to be effective, and clinical practice guidelines recommend the combination of psychosocial interventions and medication. Finally, initial studies of some types of complementary and alternative interventions have shown promise. Lack of evidence does not equate lack of efficacy, but more studies are needed in patients with cancer and diverse diagnoses before practice recommendations can be made.

Oncology nurses are ideally situated not only to assess for depressive symptoms in their patients, but also to provide education about depression and its effects, offer support, and make appropriate referrals when needed. Such actions will augment a holistic approach to high-quality care for patients with cancer.

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Caryl D. Fulcher, MSN, APRN, BC, is a clinical nurse specialist in the Department of Advanced Clinical Practice at Duke University Health System in Durham, NC; Terry Badger, PhD, APRN, BC, FAAN, is a professor and division director in the College of Nursing at the University of Arizona in Tucson; Ashley K. Gunter, BSN, RN, OCN^®, is a clinical nurse III in the Department of Adult Stem Cell Transplants at Duke University Health System; and Joyce A. Marrs, MS, APRN, BC, AOCNP^®, is a nurse practitioner and Jill M. Reese, BSN, RN, OCN^®, is a clinical nurse educator, both at Hematology and Oncology of Dayton in Ohio. No financial relationships to disclose. (Submitted April 2007. Accepted for publication October 26, 2007.)

Author Contact: Caryl D. Fulcher, MSN, APRN, BC, can be reached at caryl.fulcher@duke.edu, with copy to editor at CJONEditor@ons.org.

Digital Object Identifier:10.1188/08.CJON.131-140