Assessing and Treating Depression in Palliative Care Patients

Med/Psych Update PALLIATIVE CARE

Assessing and treating depression in palliative care patients

Antidepressants, psychotherapy can improve dying patients’ quality of life

epression is highly prevalent in hospice and palliative care settings—especially among cancer patients, in whom the prevalence of depression may be 4 D 1 times that of the general population. Furthermore, suicide is a relatively common, unwanted consequence of depression among cancer patients.2 Whereas the risk of suicide among advanced cancer patients may be twice that of the general population,3 in specific cancer populations (male patients with pancreatic adenocarcinoma) the risk of suicide may be 11 times that of the general population.4 Mental health professionals often are consulted when treating depressed patients with advanced illness, especially when suicidal thoughts or wishes for a hastened death © PALETTE7/SHUTTERSTOCK, INC are expressed to oncologists or primary care physicians. To mitigate the effects of depression among seriously ill pa- Sean Marks, MD tients (Box, page 36),5,6 mental health professionals must be Assistant Professor of Medicine Division of Hematology and Oncology able to assess and manage depression in patients with progressive, incurable illnesses such as advanced malignancy. Thomas Heinrich, MD Associate Professor and Director Division of Psychosomatic Medicine Department of Psychiatry and Behavioral Medicine Diagnostic challenges • • • • Assessing depression in seriously ill patients can be a challenge Medical College of Wisconsin for mental health professionals. Cardinal neurovegetative Milwaukee, Wisconsin symptoms of depression, such as anergia, anorexia, impaired Disclosure concentration, and sleep disturbances, also are common man- The authors report no financial relationship with any company whose ifestations of advanced medical illness.7 Furthermore, it can products are mentioned in this article or with manufacturers of competing products. be difficult to gauge the significance of psychological distress among cancer patients. Although depressive thoughts and symptoms may be present in 15% to 50% of cancer patients, only 5% to 20% will meet diagnostic criteria for major depres- Current Psychiatry sive disorder (MDD).8,9 You may find it challenging to deter- Vol. 12, No. 8 35 Box for an antidepressant or a psychostimulant, which can exacerbate delirium rather than Don’t underestimate the impact alleviate depressive symptoms. of depression in this setting Significant attitudinal barriers from both

eft untreated, depression in seriously ill clinicians and patients can lead to under- Lpatients can be associated with increased recognition and undertreatment of depres- physical symptoms, suicidal thoughts, sion. Clinicians may believe the patient’s Palliative worsened quality of life, and emotional depression is an appropriate response to distress.5 Moreover, depression can impair care the patient’s interaction with family during the dying process; indeed, feeling sad or de- a pivotal time in which patients may be pressed may be an appropriate response to saying goodbye, thank you, or planning for bad news or a medical setback, but meeting their death. Depressive symptoms even can erode the construct of patient autonomy MDD criteria should be viewed as a patho- by interfering with one’s ability to engage logic process that has adverse medical, psy- in medical decisions and attain a sense of chological, and social consequences. Time meaning from their illness.6 constraints or personal discomfort with existential concerns may prevent a clinician from Clinical Point Table 1 exploring a patient’s distress out of fear that Side effects from Questions included in Robinson’s such discussions may cause the patient to 4-point algorithm become more depressed.11 Patients may un- commonly used derreport or consciously disguise depressive 1. In the past 2 weeks, have you been worn therapeutics for 12 out or had too little energy, even when you symptoms in their final weeks of life. cancer patients can haven’t been doing a lot? mimic depressive 2. During the past 2 weeks, have you often been bothered by a lack of interest or Responding to these challenges symptoms pleasure in doing things? The Science Committee of the Association 3. In the past 2 weeks, have you been feeling of Palliative Medicine performed a thor- depressed or sad at all? ough assessment of available screening 4. In the past 2 weeks, have you talked or moved more slowly than is normal for you? tools and rating scales for depressive symp- Were you so restless that you couldn’t sit toms in palliative care. Although the com- still? mittee found that commonly used tools Source: Reference 15 such as the Edinburgh Depression Scale and the Hospital Anxiety and Depression Scale have validated cutoff thresholds for pallia- mine whether to use pharmacotherapy for tive care patients, the depression screening depressive symptoms or whether engaging tool with the highest sensitivity, specificity, in reflective listening and exploring the pa- and positive predictive value was the ques- tient’s concerns is the appropriate therapeu- tion: “Are you feeling down, depressed, or hope- tic intervention. less most of the time over the last 2 weeks?”13,14 Side effects from commonly used thera- Other short screening algorithms have peutics for cancer patients—chemothera- been validated among palliative care patients peutic agents, opioids, benzodiazepines, (Table 1).15 Endicott proposed a structured glucocorticoids—can mimic depressive approach to help clinicians differentiate symptoms. Clinicians should include hypo- MDD from common physical ailments of active delirium in the differential diagnosis progressive cancer in which physical criteria of depressive symptoms in cancer patients. for an MDD diagnosis are substituted by af- Discuss this article at Delirium is an important consideration in fective symptoms (Table 2).16 The improved www.facebook.com/ the final days of life because the condition risk-benefit ratio of selective serotonin CurrentPsychiatry has been shown to occur in as many as 90% reuptake inhibitors (SSRIs) and serotonin- of these patients.10 A mistaken diagnosis of norepinephrine reuptake inhibitors (SNRIs), depression in a patient who has hypoactive coupled with the potential significant delirium (see “Hospitalized, elderly, and morbidity associated with MDD and sub- delirious: What should you do for these pa- syndromal depressive symptoms, makes it Current Psychiatry 36 August 2013 tients?” page 10) might lead to a prescription necessary to recognize and treat those symptoms even when the cause of the depressive Table 2 symptoms is unclear. Physical depressive symptoms vs replacement psychological Psychotherapy in palliative care symptoms Psychotherapeutic interventions such as dig- Physical symptoms… nity therapy, which invites patients to utilize Change in appetite a meaning-centered life review to address his Sleep disturbance (her) existential concerns, may help depressed Fatigue 17 palliative care patients. Evidence suggests a Diminished ability to think or concentrate strong association between diminished digni- …are replaced by psychological symptoms ty and depression in patients with advanced Tearfulness, depressed appearance illness.18 Individualized psychotherapeutic in- Social withdrawal, decreased talkativeness terventions that provide a framework for ad- Brooding, self-pity, pessimism dressing dignity-related issues and existential Lack of reactivity, blunting distress among terminally ill patients could Source: Reference 16 help preserve a sense of purpose throughout Clinical Point the dying process. Surveys of dignity therapy Placebo-controlled have been encouraging: 91% of participants reported being satisfied with dignity therapy ness on the patient or family, or reduced need trials of SSRIs and and more than two-thirds reported an im- for hospitalization. Therefore, mental health SNRIs have yielded proved sense of meaning.18 professionals should consider palliative care mixed results in Other promising psychotherapeutic in- consultation for advanced cancer patients cancer patients; terventions include supportive-expressed with signs of psychological distress. differences in efficacy group therapy, in which a group of advanced cancer patients meets with a mental may not be significant health professional and discusses goals of Pharmacotherapy options building bonds, refining life’s priorities, and Antidepressants. Patients with excessive “detoxifying” the experience of death and guilt, anhedonia, hopelessness, or rumina- dying.19 A primary purpose of this therapy tive thinking along with a related impair- is not just to foster improved relationships ment in quality of life may benefit from within a group of cancer patients, but also pharmacotherapy regardless of whether within their family and oncology team, they meet diagnostic criteria for MDD. with the aim of improving compliance with Although SSRIs and SNRIs have become a anticancer therapies. Nurse-delivered, one- mainstay in managing depression, placebo- on-one sessions focusing on depression edu- controlled trials have yielded mixed results cation, problem-solving, coping techniques, in depressed cancer patients. Furthermore, and telecare management of pain and de- differences in efficacy among these antide- pression also improves outcomes among de- pressants may not be significant, according pressed cancer patients.20 to a recent meta-analysis.22 Hospital-based inpatient and outpatient Select an antidepressant based on the palliative care consultation teams are becom- patient’s past treatment response, target ing more common. A randomized controlled symptoms, and potential for adverse events. trial of early palliative care outpatient consul- Mirtazapine has relatively few drug in- tation for patients with incurable lung cancer teractions; the side effects of sedation and showed improved depression outcomes, bet- weight gain may be welcome among pa- ter quality of life, and a modest improvement tients with insomnia and impaired appetite.23 in survival.21 Although the most effective Furthermore, mirtazapine is a 5-HT3 receptor elements of a palliative care consult remain antagonist,24 which suggests it might act as unspecified and require further research, an effective antiemetic.25 Other SNRIs, such improvement in outcomes may result from as venlafaxine and duloxetine, have dem- more effective symptom management, bet- onstrated benefits in managing neuropathic Current Psychiatry ter acknowledgement of the burden of ill- pain in patients who do not have cancer.26 Vol. 12, No. 8 37 continued Table 3 Dosing recommendations for possible pharmacotherapy options Onset Starting Usual daily Maximum Drug of action dose dose daily dose Schedule

Methylphenidate <24 hours 2.5 to 5 mg 5 to 10 mg 60 to 90 mg 8 am and 12 pm Modafinil <24 hours 100 to 200 to 400 mg Single early 200 mg 300 mg morning dose Palliative care Transdermal Weeks 6 mg/d 6 to 12 mg/d 12 mg/d Daily selegiline Source: Reference 32

Psychostimulants. Patients with a progno- cancer, severe mucositis, and dysphagia. The sis of days or weeks might not have enough dose-related dietary requirements—tyra- time for an antidepressant to achieve full ef- mine restriction—and careful monitoring for Clinical Point fect. Open prospective trials and pilot stud- drug interactions may limit the use of selegi- 31 Psychostimulants ies have shown that psychostimulants can line in medically ill patients. See Table 3 for improve cancer-related fatigue and quality a list of dosing recommendations for phar- can improve cancer- of life while also augmenting the action of macotherapeutic options.32 related fatigue antidepressants.27 Psychostimulants, such Use the strategy of “start low, go slow” and quality of life as methylphenidate, have been used for when initiating and adjusting antidepres- while augmenting treating cancer-related fatigue and depres- sants because patients with cancer and other sive symptoms in medically ill patients. advanced illnesses often have concomitant the action of Their rapid onset of action, coupled with organ failure and are at risk of drug inter- antidepressants minimal side effect profile, make them a actions. Carefully review your patient’s good choice for seriously ill patients with medication list for agents that are no longer significant neurovegetative symptoms of a beneficial or possibly contributing to de- depressive disorder. Note: Avoid psycho- pressive symptoms to help reduce the risk stimulants in patients with delirium and of adverse pharmacokinetic and pharmaco- use with caution in patients with heart dynamic interactions. disease.28

Novel agents. A growing body of preclini- Requests for a hastened death cal research suggests that glutamate may be As many as 8.5% of terminally ill patients involved in the pathophysiology of MDD. have a sustained and pervasive wish for an Ketamine modulates glutamate neurotrans- early death.33 Although requests for a has- mission as an N-methyl-d-aspartate receptor tened death may evoke strong emotional antagonist. A recent evaluation of a single reactions and compel many clinicians to dose IV of ketamine in a placebo-controlled, recoil or harshly reject such requests, con- double-blind trial found that depressed sider such requests as an opportunity to patients receiving ketamine experienced gain insight into the patient’s narrative significant improvement their depressive of his (her) suffering. The clinician’s role symptoms.29 Irwin and Iglewicz30 describe 2 in such cases is to identify suicidality and hospice patients administered a single oral perform a thorough suicide risk assess- dose of ketamine, which provided rapid re- ment. Interventions to prevent suicide lief of depressive symptoms and was well should attempt to balance the seriousness tolerated. of self-harm threats with restrictions on the Transdermal selegiline may help patients patient’s liberty.34 who have trouble taking oral medications, Clinicians also need to consider the pa- including antidepressants. Inability to tol- tient’s prognosis in their decision-making. erate or absorb medications may be related For example, an extremely depressed or sui- Current Psychiatry 38 August 2013 to several conditions such as head and neck cidal patient may not benefit from psychiat- Table 4 The legality of physician-assisted suicide, euthanasia, and palliative sedation Term Definition Legality in the United States Physician- A doctor intentionally helps a person commit suicide Legal in Oregon, Washington, assisted by providing drugs for self-administration at that and Vermont by legislation and suicide person’s voluntary and competent request Montana by court ruling Euthanasia A doctor intentionally kills a person by administering Illegal drugs at the person’s voluntary and competent request Palliative Controlled administration of sedative medications Legal sedation to reduce patient consciousness to the minimum extent necessary to render intolerable and refractory suffering tolerable Source: References 35,36

Clinical Point ric hospitalization if she (he) has progressive advance care planning vs standard care in When a patient neurovegetative symptoms and a prognosis hospitalized geriatric patients found that ad- of only a few weeks to live. These situations vance care planning was more likely to lead requests a hastened often are challenging and require a careful, to end-of-life wishes that were recognized by death, a clinician’s informed discussion of the risks and benefits clinicians, and was associated with less dis- role is to identify of all proposed interventions. tress, anxiety, and depression as reported by suicidality and Clinicians also should be familiar with bereaved family members.38 perform a suicide distinctions among ethical issues in end- Clinicians can assist patients with ad- of-life care, including physician-assisted vanced care planning by helping them fill risk assessment suicide, euthanasia, and palliative sedation out advance directives, such as durable (Table 4).35,36 health care power of attorney documents In Oregon, requests for physician- and a living will. Palliative care clinicians assisted suicide and hastened death through can offer specialty-level assistance in ad- the state’s Death with Dignity Act often are vance care planning, provide focused as- short lived, and may not persist when clini- sessments of physical and psychosocial cians offer patients good symptom manage- symptoms, develop appropriate clinical ment and psychological support.37 Requests goals, and assist in coordinating individu- for a hastened death often are motivated by alized care plans for seriously ill patients.2 loss of control, inability to find meaning in death, indignity from being dependent, and References 1. Irwin SA, Rao S, Bower K, et al. Psychiatric issues in concern for future suffering and burden on palliative care: recognition of depression in patients enrolled loved ones.37 in hospice care. J Palliat Med. 2008;11(2):158-163. 2. Misono S, Weiss NS, Fann JR, et al. Incidence of suicide in Carefully evaluate requests for hastened persons with cancer. J Clin Oncol. 2008;26(29):4731-4738. death in a manner that balances your per- 3. Breitbart W, Rosenfeld B, Pessin H, et al. Depression, hopelessness, and desire for hastened death in terminally ill sonal and professional integrity. To preserve patients with cancer. JAMA. 2000;284(22):2907-2911. personal integrity, clearly communicate 4. Turaga KK, Malafa MP, Jacobsen PB, et al. Suicide in patients with pancreatic cancer. Cancer. 2011;117(3):642-647. therapeutic interventions that you can and 5. Rosenstein DL. Depression and end-of-life care for patients cannot provide. To ensure the patient does with cancer. Dialogues Clin Neurosci. 2011;13(1):101-108. 6. King DA, Heisel MJ, Lyness JM. Assessment and not feel abandoned, identify factors that psychological treatment of depression in older adults with terminal or life-threatening illness. Clin Psychol (New York). contribute to the patient’s suffering and ex- 2005;12(3):339-353. press a desire to search for alternative care 7. Block SD. Assessing and managing depression in the terminally ill patient. ACP-ASIM End-of-Life Care approaches that will be mutually accept- Consensus Panel. American College of Physicians - able to the patient and to you. American Society of Internal Medicine. Ann Intern Med. 2000;132(3):209-218. Advance care planning and palliative 8. Chochinov HM, Wilson KG, Enns M, et al. Prevalence of care consultations may help in these cir- depression in the terminally ill: effects of diagnostic criteria and symptom threshold judgments. Am J Psychiatry. Current Psychiatry cumstances. A randomized trial comparing 1994;151(4):537-540. Vol. 12, No. 8 39 continued 21. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Related Resources Engl J Med. 2010;363(8):733-742. • American Academy of Hospice and Palliative Medicine. 22. Gartlehner G, Hansen RA, Morgan LC, et al. Comparative www.aahpm.org. benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta- • Death with Dignity National Center. www.deathwithdignity. analysis. Ann Intern Med. 2011;155(11):772-785. org. 23. Kast RE, Foley KF. Cancer chemotherapy and cachexia: • National Hospice and Palliative Care Organization. www. mirtazapine and olanzapine are 5-HT3 antagonists with nhpco.org. good antinausea effects. Eur J Cancer Care (Engl). 2007; 16(4):351-354. • Oregon Health Authority. Death with Dignity Act. http:// Palliative 24. Anttila SA, Leinonen EV. A review of the pharmacological public.health.oregon.gov/ProviderPartnerResources/ and clinical profile of mirtazapine. CNS Drug Rev. 2001; care Evaluationresearch/deathwithdignityact/Pages/index.aspx. 7(3):249-264. Drug Brand Names 25. Pae CU. Low-dose mirtazapine may be successful treatment option for severe nausea and vomiting. Prog Duloxetine • Cymbalta Modafinil • Provigil Neuropsychopharmacol Biol Psychiatry. 2006;30(6): Ketamine • Ketalar Selegiline (transdermal) 1143-1145. Methylphenidate • EMSAM 26. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. • Concerta, Ritalin Venlafaxine • Effexor Cochrane Database Syst Rev. 2007;(4):CD005454. Mirtazipine • Remeron 27. Pereira J, Bruera E. Depression with psychomotor retardation: diagnostic challenges and the use of psychostimulants. J Palliat Med. 2001;4(1):15-21. 28. Jackson V, Block S. # 061 Use of Psycho-Stimulants in Clinical Point Palliative Care, 2nd ed. End of Life/Palliative Education Resource Center. Medical College of Wisconsin. http:// 9. Massie MJ. Prevalence of depression in patients with cancer. www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_061.htm. J Natl Cancer Inst Monogr. 2004;(32):57-71. Clinicians can Accessed December 28, 2012. 10. Spiller JA, Keen JC. Hypoactive delirium: assessing the 29. Berman RM, Cappiello A, Anand A, et al. 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Bottom Line Depression commonly is encountered in hospice and palliative care patients and is associated with morbidity and distress. Validated screening tools can help you distinguish major depressive disorder from depressive symptoms in this population. Several psychotherapeutic techniques have been shown to be beneficial. In addition to traditional antidepressants, psychostimulants or ketamine may help Current Psychiatry 40 August 2013 address acute depressive symptoms in patients who have days or weeks to live.