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Meaning-Centered Psychotherapy and Cancer

Cancer can lead to suffering in many forms: physical, emotional, spiritual, and existential. It limits patients’ ability to plan for the future and, too often, their lives. How can we help patients cope with their suffering and existential distress in the face of such challenges? Meaning-Centered Psychotherapy (MCP) may have something to offer. MCP is a brief, structured, manualized intervention that organizes and distills existential concepts so that they are more accessible and relevant to patients’ lives. Born out of research demonstrating that meaning can serve as a buffer against the depression and hopelessness that many patients with metastatic disease report, Breitbart and colleagues developed MCP to help enhance patients’ sense of 

and purpose in the face of advanced cancer.

 specific concepts highlighted in MCP include:

: There is always the possibility of creating or experiencing meaning, even in the last moments of life. The feeling that “life is meaningless” therefore reflects a disconnection from what gives our lives meaning.

 The desire to find meaning in our existence is a primary motivating force in human behavior that drives us to search for and create meaning throughout our lives.

We have the freedom to choose how to think about and respond to what comes our way, including limitations, challenges, losses, and uncertainty. This is a core concept in MCP, as the ability to choose our attitude toward suffering is something we always have control over, even in the worst of circumstances.

 A sense of meaning can be derived from connecting to sources of meaning, including those described in MCP as historical, attitudinal, creative, and experiential (see 

Guided by structured questions in each session, MCP helps patients systematically reflect on what matters most to them and how sources of meaning can be accessed during challenging times. If a given source of meaning is not accessible, because of physical limitations or concerns about contracting 

, for example, MCP therapists brainstorm with patients about how to tap into the meaningful aspects of these activities or experiences in adapted forms. Therapists repeatedly highlight sources of meaning in the patient’s life that can be used as resources to buoy the patient during difficult moments.

This is the sentiment behind Nietzsche’s quote, “He who has a Why to live for can bear almost any How” that Frankl often referenced. In essence, MCP helps patients connect to their “Whys”—that is, their reasons for living—despite the suffering they endure. Frankl viewed suffering as a potential springboard for seeking and finding meaning. Patients’ drive to make sense of the challenges they face may lead to growth and identification of positive sequelae that can emerge as a byproduct of their adversity.

However, therapists should be clear that MCP is not a prescription for turning lemons into lemonade; instead it provides an opportunity to reflect on patients’ free will, highlighting adaptive perspectives as a choice in attitude. Therapists guide the development of a coherent narrative about how meaning and values influenced past choices, which can help address regrets. The enhanced sense of meaning resulting from such processes can improve patients’ quality of life and reduce distress.

Research demonstrating the efficacy of MCP

MCP has demonstrated efficacy in enhancing meaning in the lives of patients with advanced cancer in several large-scale trials and has been designated a National Cancer Institute Research-Tested Intervention Program. In 2 randomized controlled trials (RCTs) with patients who had advanced cancer, Meaning-Centered Group Psychotherapy (MCGP; an 8-session version of MCP) demonstrated efficacy over supportive group psychotherapy in improving spiritual well-being, quality of life, and sense of meaning, as well as decreasing anxiety, hopelessness, and desire for hastened death.

While MCGP showed efficacy, challenges with attrition in groups prompted development of an individual format that would allow for more flexible scheduling for patients.

 Thus, the 7-session format of Individual Meaning-Centered Psychotherapy (IMCP) was developed.

 In a pilot RCT comparing IMCP to therapeutic massage, participants receiving IMCP experienced significantly greater improvement in spiritual well-being, symptom burden, and distress.5 There was also less attrition compared with MCGP trials. A larger- scale RCT of IMCP demonstrated its superior efficacy in improving quality of life and sense of meaning compared with Supportive Psychotherapy and Enhanced Usual Care (see 

 IMCP also resulted in greater reductions in anxiety and desire for hastened death than Enhanced Usual Care. These studies provide strong support for the efficacy of both MCGP and IMCP in treating psychological and existential distress among patients with advanced cancer.

MCP should be delivered in the context of a supportive therapeutic relationship; an exploration of how to find meaning in suffering can only work effectively when the therapist acknowledges, supports, and validates the patient’s suffering. The structured nature of MCP, which includes a combination of didactics, experiential exercises, and guided discussion, enables the deep exploration of powerful concepts in a short period of time (

). MCP capitalizes on its time-limited format to propel patients to engage with emotionally provocative topics and take steps toward addressing unfinished business. MCP concludes with a Legacy Project to encourage patients to connect to sources of meaning and actively engage in something they have wanted to do but have not yet done.

Each MCP session introduces key existential concepts followed by an experiential exercise to help patients apply these concepts to their lives. Patients are encouraged to reflect on the exercise before the session, in writing if possible. Ultimately, the goal is for the sources of meaning identified to serve as coping resources that patients can continue to draw upon after therapy has concluded. Patients’ ability to shift from one source of meaning to another is emphasized, as some sources may become less available due to disease progression. Therapists support the concept of moving from ways of doing to ways of being to assist patients to recognize that meaning can also be derived more passively.

Additional existential concepts, including responsibility, transformation, authenticity, and existential guilt are also woven throughout the treatment. Therapists assist to detoxify death by speaking openly about it as the ultimate limitation in life, which is directly discussed in the session on attitudinal sources of meaning. They may challenge a patient’s resistance to exploring difficult existential realities, such as death or existential guilt, by using a gentle “existential nudge” to encourage reflection. In addition to facilitating the exploration of sources of meaning and existential concepts, the therapist plays a powerful role in enhancing the impact of MCP by witnessing the patient’s suffering, unique legacy, identity, and sense of meaning. Thus, the therapist becomes another figure through which patients can experience meaningful connection and share their “living legacy.” Therapists are encouraged to offer genuine reflections throughout MCP about patients’ meaningful impact on them, which can be particularly powerful for socially isolated patients.

Because MCP focuses on the universal struggles with existential distress in illness, it is not linked to a specific psychiatric diagnosis. MCP is not designed to treat acute psychiatric symptoms (eg, 

); therapists should refer patients to first-line stabilizing treatment (eg, medication) prior to attempting MCP. Patients with sufficient physical or cognitive limitations (eg, advanced dementia) to preclude participation in psychotherapy are not suited for this intervention. In research, MCP has demonstrated particular efficacy in improving outcomes in patients with moderate to severe distress (scoring 4 or higher on the Distress Thermometer).

The individual and group formats of MCP are nearly identical in content but differ in length. MCGP has 8 sessions, providing additional time to focus on the historical sources of meaning, which involves patients sharing about their past, present, and future legacy. In MCGP, group members each share responses to the experiential exercises and commonalities are emphasized. Group facilitators acknowledge the “co-creation of meaning” between themselves and group members; everyone present becomes witnesses, or repositories of meaning, for each other, and thus are part of a meaningful legacy created within the group.

In facilitating MCGP groups, the basic tenets of group processes remain important.

 Facilitators should intentionally honor each member’s unique values. IMCP is structured similarly yet affords more flexibility and the opportunity to deepen the meaning-centered work with fewer time constraints. Ideally patients should attend all sessions to get the maximum benefit, as there is a logical progression of content. However, in-person attendance is not necessary as MCP has been successfully 

“Dr Smith” was a 40-year-old, married physician with one child who began MCP shortly after he received a diagnosis of advanced pancreatic cancer. Although skeptical of how meaning could help him, Dr Smith was hoping for relief from the overwhelming distress he was experiencing about his diagnosis. He was particularly upset by changes in his ability to work as a physician and fulfill responsibilities to his wife, children, and aging parents.

During Session 2, Identity Before and After Cancer, it became clear that being suddenly thrust into the patient role threatened Dr Smith’s sense of identity as someone who provides care for others and strives for perfection. While Dr Smith acknowledged gaining a greater understanding of the existential nature of his distress through discussion, he expressed frustration that there was no way to “fix” this suffering.

In Session 3, Historical Sources of Meaning, the concept of legacy proved to be the key to shifting the meaning Dr Smith made of his current struggles. He realized the distress around perceived changes to his identity were connected to the legacy he was given, as he had been encouraged by his family to be perfect and “fix things.” He realized he could choose to respond differently to the legacy he was given, leading to changes in how he parented and allowing things to be imperfect and messy more often.

As sessions progressed, ways that Dr Smith creatively responded to the physical challenges he faced were identified, reinforcing the concepts of choice and courage in how he faced his predicament. This included the choice to engage in MCP despite his skepticism and to accept help from others, which became a meaningful lesson he wanted to model for his child. In his final session, Dr Smith expressed feeling more connected to the people who mattered most to him, recognizing new ways he could continue to share his legacy of responsibility and caregiving with those whose lives he touched personally and professionally.

Given its demonstrated efficacy, efforts are underway to disseminate MCP by training clinicians who work with cancer patients through a National Cancer Institute-funded training program. Additionally, many replication and adaptation studies are ongoing, including efforts to adapt MCP for cancer survivors, parents bereaved by cancer, cancer caregivers, and patients in hospice.

 Cultural and linguistic adaptations have also been conducted.

MCP may be especially helpful in working with patients struggling with adversity and situations that feel beyond their control. This may be more relevant than ever in context of the 

 pandemic, which, in threatening lives and imposing limitations on access to sources of meaning, has increased existential distress for patients, caregivers, and health care providers. Patients living through the pandemic are facing isolation, restrictions on their freedom, personal losses, and even greater threats to their and their loved ones’ mortality than they have previously experienced.

MCP empowers patients to focus on the choices they have in the face of limitations, helping them to connect to what matters most. It reaffirms the idea that meaning is always possible. When we are feeling disconnected, MCP facilitates reconnection. Therapists from a variety of theoretical orientations may find it helpful to draw on MCP concepts to support individuals through these uncontrollable and extraordinary circumstances. In turn, we derive meaning from the uniquely reciprocal nature of MCP, in that, as we accompany patients in their exploration of meaning, we co-create meaningful connection and our own personal legacies.

 is Assistant Attending Psychologist, Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, and Assistant Professor of Psychology, Department of Psychiatry, Weill Cornell Medicine; 

 is Postdoctoral Research Fellow, Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center; 

 is Research Project Manager, Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center; 

 Assistant Attending Psychologist, Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, and Assistant Professor of Psychology, Department of Psychiatry, Weill Cornell Medicine; and 

 is Chair, Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, and Professor of Clinical Psychiatry, Department of Psychiatry, Weill Cornell Medicine. The authors report no conflicts of interest concerning the subject matter of this article.

Research on MCP has been supported by the National Cancer Institute (R01 CA128187, R01 CA128134, R25 CA190169, T32 CA009461, P30 CA008748), the National Institute of Nursing Research (R21 AT01031), The Fetzer Institute, and the Kohlberg Foundation.

1. Breitbart W, Rosenfeld B, Pessin H, et al. Depression, hopelessness, and desire for hastened death in terminally ill patients with cancer. 

2. Nelson CJ, Rosenfeld B, Breitbart W, Galietta M. Spirituality, religion, and depression in the terminally ill. 

3. Breitbart W, Gibson C, Poppito SR, Berg A. Psychotherapeutic interventions at the end of life: a focus on meaning and spirituality. 

Meaning-Centered Psychotherapy in the Cancer Setting: Finding Meaning and Hope in the Face of Suffering

. New York, NY: Oxford University Press; 2017.

5. Breitbart W, Poppito S, Rosenfeld B, et al. Pilot randomized controlled trial of individual meaning-centered psychotherapy for patients with advanced cancer. 

6. Breitbart W, Rosenfeld B, Gibson C, et al. Meaning-centered group psychotherapy for patients with advanced cancer: a pilot randomized controlled trial. 

7. Breitbart W, Rosenfeld B, Pessin H, et al. Meaning-centered group psychotherapy: an effective intervention for improving psychological well-being in patients with advanced cancer. 

. Revised ed. New York: Washington Square Press; 1959/1984.

10. Applebaum AJ, Lichtenthal WG, Pessin HA, et al. Factors associated with attrition from a randomized controlled trial of meaning-centered group psychotherapy for patients with advanced cancer. 

11. Breitbart W, Pessin H, Rosenfeld B, et al. Individual meaning-centered psychotherapy for the treatment of psychological and existential distress: a randomized controlled trial in patients with advanced cancer. 

Individual Meaning-Centered Psychotherapy for Patients With Advanced Cancer: A Treatment Manual

Meaning-Centered Group Psychotherapy for Patients With Advanced Cancer: A Treatment Manual

14. NCCN. Distress management: Clinical practice guidelines. 

The Theory and Practice of Group Psychotherapy

16. Lichtenthal W, Roberts K, Jankauskaite G, et al. Meaning-centered group psychotherapy for breast cancer survivors. Breitbart W, Ed. 

Meaning-Centered Psychotherapy in the Cancer Setting

. New York, NY: Oxford University Press; 2017: 54-66.

17. Lichtenthal WG, Catarozoli C, Masterson M, et al. An open trial of Meaning-Centered Grief therapy: rationale and preliminary evaluation. 

18. Applebaum AJ, Kulikowski JR, Breitbart W. Meaning-centered psychotherapy for cancer caregivers (MCP-C): rationale and overview. 

19. Rosenfeld B, Saracino R, Tobias K, et al. Adapting Meaning-Centered Psychotherapy for the palliative care setting: results of a pilot study. 

An added component of cancer treatment is discovering what is most meaningful in the patient’s life and using that to buoy them during difficult moments. That, in a nutshell, is the psychiatrist's role.

Finding Meaning in the Face of Suffering

Here: A summary of indicators for stress and anxiety in patients undergoing transplantation, and why it is important for psychiatrists to be aware of these factors.

Key Stressors in Transplant Psychiatry

The challenges of a busy neuropsychiatric practice give us opportunity to further explore real world applications of our current armamentarium. This is true regarding both pharmacology as well as other procedural interventions. The following case will hopefully highlight some of these challenges as well as opportunities.

The patient originally presented as a 33-year-old man with a history of polysubstance abuse and mood disorder. He had been referred for neuropsychiatric assessment by our migraine clinic. Unfortunately, he received his third driving while intoxicated citation and failed drug court, and he was slated for incarceration. A few days prior, he received a diagnosis of Huntington disease (HD) by one of our movement disorder specialists. He was placed in a medium security facility where his condition was treated with a combination of aripiprazole, duloxetine, and hydroxyzine. Nonetheless, he described experiencing both visual and auditory hallucinations. The visual hallucinations were quite dramatic, involving zombies with pieces of their flesh falling off. The auditory hallucinations were not of a command nature and involved deprecating, condescending, and derogatory statements regarding the patient.

He was released after approximately 2 years, with 3 years of probation. His medications were abruptly discontinued 3 months before his release, and he was placed on haloperidol. The patient reported that these had not been particularly effective. Fortunately, he was also involved in the recovery process, and attended Narcotics Anonymous meetings twice weekly and visited an outpatient addiction clinic at least weekly.

His movement disorder specialist then prescribed deutetrabenazine for HD. The neuropsychiatry team discontinued haloperidol and began treatment with 34-mg pimavanserin daily. After 4 weeks, he noted an amelioration of the auditory hallucinations. Mood continued to be a problem (PHQ-9 = 20); lamotrigine was started with the customary 5-week titration schedule. After 2 more weeks, the patient reported amelioration of auditory and visual hallucinations.

The vicissitudes of life continued to take their toll on the patient, including some conflicts regarding custody of his 6-year-old son. The patient began to experience drug cravings and was started on 

. At the time, he began to describe ideas of reference, receiving messages through the television. The decision was made to increase pimavanserin to 51 mg daily. The patient was made aware that this was above the usual US Food and Drug Administration dosing guidelines; after a discussion of the benefits, alternatives, and risks, he decided to proceed.

Four weeks later, the patient reported a significant amelioration of his psychosis. He also indicated he was essentially more sociable, was spending more time with his son, and was participating in community activities. In fact, his parole officer extended the time between reporting from weekly to every 3 weeks. The auditory hallucinations resolved completely; the visual hallucinations continued to ameliorate and resembled illusions.

The treatment was managed with 17-mg pimavanserin samples. When manufacturing of 17-mg pimavanserin samples stopped, the patient’s dose was reduced to 34 mg daily. Subsequently, the patient experienced an exacerbation of both auditory and visual hallucinations. Due to a lack of available samples and repeated denials of coverage by his insurance company, pimavanserin was discontinued and he was treated with other antipsychotics. Trials of adequate dose and duration with quetiapine and cariprazine did not result in amelioration of psychotic symptoms. The patient also began to miss visits and to follow-up less frequently.

Eleven months later, through a combined effort of both neuropsychiatry and movement disorder neurology, the patient once again was treated with 34-mg pimavanserin. Eight weeks later, he described the near resolution of auditory hallucinations, a significant amelioration of visual hallucinations, and some occasional paranoid thought content. His regimen was augmented with 25-mg 

daily. One month later, during a follow-up visit, the patient described complete resolution of auditory hallucinations and delusions. His visual hallucinations, although greatly ameliorated, persisted. Clozapine was increased to 50 mg, which resulted in full resolution of symptoms.

A variety of studies were conducted during the early course of his evaluation and treatment, including an electroencephalogram, multiple sleep latency test, extensive lab work, and electromyography, and neuroimaging of the brain and spine. Most results were within normal limits or essentially benign. He had a polysomnography indicative of 

This patient exemplifies the complicated nature of neuropsychiatric practice. Taking into account the pre-existing movement disorder with rather significant comorbid psychiatric problems (including a higher risk of suicide) associated with HD, we were not eager to treat him with the usual dopamine blockade. Pimavanserin seemed ideally suited for the situation. When that medication is not enough to eradicate psychosis and some form of dopaminergic agent is inevitable, the 

An argument can certainly be made that 68-mg pimavanserin would be preferable to the addition of a dopamine blocking agent. However, this would undoubtedly precipitate a conflict with the patient’s managed care insurance carrier.

Treatment utilizing the biopsychosocial model, including 12-step programs and addiction counseling, is indispensable. In addition, incarceration in this case dovetailed with recovery. In other words, the neuropsychiatric skill set must not be devoid of humanism. While science and technology expand our abilities, our goals still revolve around the patient and maximizing function.

Here, we see the role of the clinician as a patient advocate and navigator of a rather complicated medical system. This included interactions with the legal system as well as various substance treatment providers.

In the final analysis, this patient’s life continues to be difficult. However, he is able to function and to act positively in terms of his commitment to others, particularly his son.

 is Medical Director, Division of Neuropsychiatry, Dent Neurologic Institute, he is also Medical Director, Addiction Services, Brylin Hospital, Buffalo, NY; 

 is Physician Assistant, Dent Neurologic Institute. The authors report no conflict of interest concerning the subject matter of this article. The patient has agreed to have his case discussed in this article.

1. Seppi K, Chaudhuri KR, Coelho M, et al. 

Update on treatments for nonmotor symptoms of Parkinson disease: an evidence-based medicine review

When the patient has significant comorbid psychiatric problems, high risk of suicide, and Huntington disease, the role of clinician spills over into patient advocate in a complex medical system.

A Double Whammy: Psychosis and Huntington Disease

Despite advances in clinical care for patients with cancer, distress and depression continue to haunt patients. These fast facts will help you better understand and care for patients with cancer. 

5 Fast Facts for Addressing Distress & Depression in Cancer

A diagnosis of cancer is life changing. Patients with cancer not only experience the physical consequences of the disease and treatment, but may also experience significant emotional distress and impairment in social functioning. Distress is 

as a “multifactorial, unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social and/or spiritual nature that may interfere with the ability to cope with cancer, its physical symptoms, and treatment.”

 It extends along a continuum ranging from common feelings of vulnerability, sadness, and fear to problems that can become disabling, such as depression, anxiety, panic, social isolation, and existential and spiritual crisis.

Distress and depression are associated with adverse outcomes including reduced quality of life, longer rehabilitation time, poor adherence to treatment, and worse survival.

 Cancer patients with depression have been shown to have four times the mortality rate compared with cancer patients without depression when adjusting for age, performance status, and cancer stage.

 Given the negative impact of distress and depression on patients with cancer, timely and accurate detection and treatment of symptoms is essential.

Distress is common in patients with cancer. Studies have shown that 30% to 50% of cancer patients experience distress and that rates of distress can vary based on age, gender, race, cancer site, and stage of disease. Carlson and colleagues examined the prevalence of distress in more than 50 cancer centers across the United States and found that patients who were female, middle-aged (40 to 59 years old), and had either pancreatic or lung cancer were more likely to be distressed.

 High rates of distress have also been demonstrated in patients with head and neck cancer and brain tumors.

 Depression is also prevalent in patients with cancer and has been identified as the most common mental health complication of cancer—a recent study showed that the odds of being depressed among cancer patients was five times higher than in the general population.

Rates of depression in patients with cancer vary widely in the literature. A critical review by Caruso and colleagues

 on the prevalence of depression showed rates of depression and depressive disorders between 5% and 60%. This variability was attributed to studies utilizing different diagnostic criteria for depression, diverse instruments/tools to identify depression, as well as the inclusion of different cancer types, stages of disease, and phases of treatment. A recent large epidemiological multi-center study demonstrated that about one in four patients (24%) with cancer is depressed (PHQ-9 ≥ 10).6 Depression also varies by cancer site and has been shown to be highly associated with brain, pancreas, head and neck, lung, breast, and gynecologic cancers.

Screening and assessment of distress and depression

While distress screening by cancer centers is required by the 

American College of Surgeons Commission on Cancer

, screening alone is insufficient and must be accompanied by referral for evaluation and treatment by a trained professional. Several scales have been identified to aid in accurate symptom assessment and are essential to methodologically screen for symptoms of distress and depression, rate symptom severity, and monitor treatment over time.

The Distress Thermometer and Problem List

 is a commonly used, validated screening tool that requires patients to rate their distress on a scale from 0 (ie, no distress) to 10 (ie, extreme distress). Scores of 4 or higher are indicative of clinically significant distress levels. An accompanying Problem Checklist prompts patients to identify any of 39 issues commonly experienced by cancer patients. These problems are grouped into 5 categories (practical, family, emotional, spiritual/religious concerns, and physical), with patients asked to report on items that have been problematic for the past week.

(HADS) and Patient Health Questionnaire (PHQ-9) are commonly utilized.

 Of course, no screening tool is a replacement for a comprehensive clinical evaluation of the patient, which should also evaluate for any reversible disease and/or treatment factors, such as those listed in 

, that may be contributing to the patient’s current presentation.

Given the prevalence and adverse outcomes associated with distress and depression in patients with cancer, identifying and utilizing effective interventions is essential. A comprehensive approach in caring for cancer patients with distress and depression should also address any medical, disease-related and/or psychosocial factors contributing to symptoms. To guide selection of treatment intervention, the 

 (NCCN) has identified Clinical Practice Guidelines (v3.2019) for managing symptoms across the continuum of distress.

 The NCCN highlighted a multidisciplinary approach based on the severity and nature of distress, with clinically significant distress prompting referral to mental health, social work, and/or chaplaincy care. The NCCN Guidelines also identified key evidence to support the use of psychosocial interventions, pharmacologic therapies, and certain practices associated with complementary and/or integrative medicine for distress and depression.

Psychosocial care, aimed at relieving emotional distress and improving patients’ well-being, is an important component in providing comprehensive care for patients with cancer. Interventions to promote psychosocial well-being are varied and can include peer support, psychoeducation, self-care promotion, and counseling/psychotherapy. An extensive review by the National Academy of Medicine demonstrated substantial evidence to support the role of psychosocial interventions in cancer care.

 demonstrated that psycho-oncology interventions, including individual psychotherapy, group psychotherapy, psychoeducation, and relaxation training, produced a significant small-to-medium beneficial effect on distress and quality of life. They also found that studies that preselected patients for intervention based on increased baseline levels of distress demonstrated a beneficial treatment effect of significantly greater magnitude.

There is a substantial body of evidence to support the use of highly tailored and manualized psycho-oncology interventions. These interventions have not only been shown to be associated with reduced distress and depression, but have also led to improved health and treatment-related behaviors and biological outcomes.

 also concluded that there is significant and clinically relevant evidence to support the use of psychotherapy for depression.

 Because of the lack of evidence to support one modality over another, selection of type of psychotherapy is recommended to be based on patient factors and available resources. Please refer to 

 for a review of some of the commonly utilized and evidence-based psychotherapy modalities.

Psychoeducational interventions are also beneficial for distress and depression.

 Exercise is an important psychoeducational intervention that has been identified as beneficial both from a physical and emotional perspective in patients with cancer.

 International Multidisciplinary Roundtable in 2018 identified exercise as being generally safe for cancer survivors, that every survivor should avoid inactivity, and that there is strong evidence to support that “specific doses of aerobic, combined aerobic plus resistance training and/or resistance training could improve common cancer-related health outcomes including anxiety, depressive symptoms, fatigue, physical functioning and health-related quality of life.”

Psychotropic medications are commonly used in patients with cancer.

 Antidepressants in particular are widely prescribed and utilized not only for depression, but often to target hot flashes, neuropathic pain, insomnia, anxiety, and appetite disturbances associated with cancer diagnosis and treatment. Recent findings suggest that psychopharmacologic treatment is efficacious in treating depression in patients with cancer; although, additional research is needed as other research has demonstrated conflicting evidence.

 The NCCN Clinical Practice Guidelines v3.2019 identified a role for pharmacotherapy in symptom management of both distress and depression. However, Li and colleagues recommended utilizing antidepressants only in moderate to severe depression or if subthreshold/mild depressive symptoms did not respond to initial therapies or were interfering with engaging in cancer treatment.

When selecting a medication to treat symptoms of severe distress or depression in patients with cancer, it requires careful consideration of several factors including the patient’s medical comorbidities, drug-drug interactions, route of administration (ie, patient with mucositis who cannot take oral medication), onset of action, profile of concurrent physical symptoms (eg, pain, insomnia, agitation, hot flashes) and adverse effect profile of the medication. Antidepressants utilized in patients with cancer are similar to those used in regular clinical practice; selective serotonin reuptake inhibitors/selective serotonin-norepinephrine reuptake inhibitors are often first line as they are well-tolerated and safe. Other antidepressants commonly utilized include mirtazapine, bupropion, tricyclic antidepressants, and psychostimulants (specific indications are briefly reviewed in 

Drug-drug interactions: a closer look at tamoxifen

Tamoxifen is a standard adjuvant therapy in breast cancer. With high rates of depression in breast cancer and hot flashes being associated with tamoxifen, antidepressants are commonly used in this patient population. However, tamoxifen is a prodrug that requires metabolism by CYP 2D6 to its active metabolite endoxifen, which has important implications on the antidepressant chosen. A strong CYP 2D6 inhibitor such as paroxetine or fluoxetine could decrease levels of endoxifen and potentially decrease the efficacy of this therapy.

 There is conflicting evidence in the literature with regards to the clinical consequence of this, with one study showing an increased risk of death from breast cancer in women taking paroxetine, although a similar risk was not identified in other studies.

 Recommendations remain to avoid use of medications that can significantly inhibit CYP 2D6 metabolism including paroxetine, fluoxetine, duloxetine, and bupropion. Preferentially utilize antidepressants with lesser degrees of CYP 2D6 inhibition including venlafaxine, escitalopram, citalopram and sertraline.

Complementary and/or integrative medicine

More than 50% of cancer patients incorporate complementary medicine into their treatment plan for symptom management and promotion of overall well-being.

 Thus, it is important that the conventional medical system provide patients with evidence-based information and guidance regarding these approaches, which can include natural products and mind and body practices. A systematic review by the 

, which looked at the effect of a number of varied complementary therapies in patients with breast cancer during and after cancer treatment, 

• Meditation, relaxation, yoga, massage, and music therapy for depression/mood disorders;

• Music therapy, meditation, stress management, and yoga for anxiety/stress reduction;

• Meditation and yoga to improve quality of life.

While complementary therapies have been most often studied in patients with breast cancer, there are data to support their use in other types of cancers. A review demonstrated benefit associated with use of mind and body practices in patients with lung cancer as part of a multidisciplinary approach to reduce mood disturbances, sleep problems, pain, and improve quality of life.

 Based on available evidence, the NCCN Clinical Practice Guidelines recommends the use of relaxation, meditation, and creative therapies such as art and music for patients experiencing distress.

Distress and depression are prevalent in patients with cancer and are associated with adverse outcomes. All patients with a diagnosis of cancer need to be screened for distress, which must be followed with referral to appropriately trained professionals and evidence-based treatment of any symptoms or problems.

Psychosocial and pharmacologic interventions are effective in reducing symptoms of distress and depression as well as improving quality of life in patients with cancer. Use of some complementary and/or integrative medicine practices is supported by the literature to address distress and depression in cancer patients.

 is Assistant Professor, Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI; 

 is Associate Professor, Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, and Associate Professor, Departments of Medicine and Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI. The authors report no conflicts of interest concerning the subject matter of this article.

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Distress and depression are associated with adverse outcomes in patients with cancer, including reduced quality of life, longer rehabilitation time, poor adherence to treatment, and worse survival.

Reducing Distress and Depression

Fears about the overprescription of opioid analgesics and the opioid epidemic have resulted in initiatives for physicians to prescribe these medications more judiciously. However, new concerns about patients needlessly suffering untreated or undertreated pain have been raised.

Unfortunately, many lay people and even many health care providers still believe that opioids are the optimal treatment for all forms of pain and that there are no good alternatives. Studies, however, have shown that nonopioid pharmacologic therapies and nonpharmacologic therapies can be as effective and, in many cases, even more effective than opioids.

and meta-analysis of mind-body therapies (MBTs) for patients whose pain is being treated with opioids highlights how useful these modalities can be and the importance of considering them when caring for patients suffering with pain.

The review included 60 studies with 6404 participants. A variety of MBTs were employed, including meditation, hypnosis, relaxation, guide imagery, therapeutic suggestion, and cognitive-behavioral therapy (CBT) depending on the individual studies. The types of pain varied from procedural pain to burn pain to cancer-related pain to chronic pain. The impact of various MBTs on the pain and on the use of opioids were examined.

The findings indicated that meditation, hypnosis, therapeutic suggestion, and CBT were most likely among the MBTs to provide the greatest pain relief with moderate to large improvements. Meditation, hypnosis, and CBT appeared to have the greatest impact on opioid use. The researchers noted that the lack of evidence for the impact of the other MBTs may reflect that there were fewer studies rather than evidence that those MBTs are less likely to have an effect on either the pain or opioid use.

There were also indications that MBTs may provide some benefit for opioid craving and misuse, another reason why their use should be considered for patients on opioids for whom it is believed these medications should be discontinued.

There were differences between the types of pain for which the individual MBTs were studied. Studies that looked at meditation-based therapies primarily focused on chronic noncancer pain while most hypnosis, relaxation, and imagery studies focused on acute, procedural, or cancer-related pain. Whether this provides any guidance as to which type of therapy would be most beneficial for which type of pain is open to question and warrants further study.

It is worth noting that there is a great deal of overlap between many of the MBTs and what might be considered meditation by some could be considered relaxation or even hypnosis by others, so there is often a lack of clear demarcation between them. MBTs are not a magic bullet for the management of pain. They showed a moderate but statistically significant effect on the pain and resulted in a small but statistically significant reduction in opioid use.

In addition to these apparent benefits, MBTs also have one very significant advantage over many of the other treatments for pain: they are essentially free of adverse events. If they are tried and do not provide any benefit, the patient will be no worse off. As with all the other interventions to manage pain, no one can guarantee that MBTs will provide improvement but one can be as close as possible to certainty that they will not have any negative impact on those being treated with them. If the opioid epidemic has taught us anything it is that therapies initiated to help patients can end up having a destructive effect.

There is one very real limitation in the introduction of the MBTs as major treatments for pain. For the most part, in academic centers and hospitals, pain management is primarily considered to be a subspecialty of a single medical specialty—anesthesiology. The only significant exception to this is headache management, which is usually considered to be a part of neurology.

The reality is that few anesthesiologists and neurologists, even those who specialize in pain management, receive much, if any, training in the use of MBTs, nor do most primary care physicians upon whom the management of pain often falls. Thus, most patients with pain are unlikely to come into contact with caregivers who are knowledgeable about MBTs, much less know how to utilize them.

Obviously, the physicians most likely to be trained in the use of MBTs are psychiatrists, and this is one of many reasons why psychiatrists should be more involved in the care for patients with all forms of pain and not just those patients with diagnosable mental disorders.

There is a need for more and better studies on MBTs for pain. However, this can be said of all the other treatments for it. Let us recall that millions of patients have been prescribed opioids for the management of chronic pain although there are virtually no studies demonstrating their efficacy.

1. Garland EL, Brintz CEE, Hanley AW, et al. 

Mind-body therapies for opioid-treated pain: a systematic review and meta-analysis

This article was originally posted on February 20, 2020, and has since been updated. -Ed

For the millions of patients whose pain is being treated with opioids, mind-body interventions are proving to be important considerations to ease suffering.

Mind-Body Therapies for the Management of Pain: How Effective Are They?

Pain is a subjective complaint for which health care professionals largely depend upon self-report by patients. However, we face a special challenge in determining whether pain is present, its severity if it is, and how it is responding to treatment in patients who are cognitively impaired. A recent review of the problem of pain among patients who suffer 

 identifies many of these issues and current recommendations for addressing them.

How do you determine whether pain is present and its severity as well as how it responds to treatment in patients who are cognitively impaired? Some answers to these questions.

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