Improving Treatment of Depression in Patients With Cancer: The SMaRT Oncology-2 Trial

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William Breitbart, MD

Yesne Alici, MD

These [psycho-oncology] programs are critically important and should be increasingly used to aid oncologists in the care of their patients with depression or other forms of psychological distress that often interfere with treatment adherence or completion of treatment.

—William Breitbart, MD, and Yesne Alici, MD

Clinical depression is highly prevalent, associated with significant morbidity, often underrecognized, and inadequately treated in cancer patients.  Professor Michael Sharpe and Jane Walker, PhD, and their colleagues’ seminal work on enhancing treatment of depression in cancer patients using a collaborative practice model—in the SMaRT Oncology-2 Trial—is thus a great step forward in this setting.1

Most studies report rates of depression in cancer patients at two to three times that seen in the general population.2 Walker and colleagues recently published data on prevalence of major depression among 21,151 patients in cancer clinics in Scotland.2 The point prevalence of major depression was highest in patients with lung cancer (13.1%), followed by gynecologic cancer (10.9%), breast cancer (9.3%), colorectal cancer (7.0%), and genitourinary cancer (5.6%). Similarly, two meta-analyses reported prevalence rates of 16% and 13% of depression for patients with all types of cancer.3,4

Depression in patients with cancer is associated with significant morbidity and increased health-care costs.5 Worse pain, anxiety, fatigue, treatment adherence, and overall functioning have been reported among depressed cancer patients,5,6 and suicide and desire for hastened death are highly prevalent.7  An example of underrecognition and inadequate treatment is provided by a recent study showing that 73% of cancer patients with major depression were reported not to have had any treatment for their depression.2

Recognition an Important First Step

Such data are of significant concern and highlight the need for more effective approaches to the management of depression in the oncology setting. There are a number of barriers to assessment and management of depression in oncology clinics. The American College of Surgeons’ Commission on Cancer has recently mandated that, as of 2015, all cancer centers in the United States screen patients for psychosocial distress.8 This represents an important step towards improving screening, assessment, and recognition of depression in oncology settings.

Development of effective management approaches for cancer patients with depression is an important next step.  Collaborative care interventions have evolved out of the need to assess and manage depression better among the medically ill. These interventions integrate a number of components into the medical setting to improve assessment and management of depression for such patients. The interventions typically include a systematic psychiatric assessment, use of a non-physician care manager responsible for monitoring depressive symptoms, treatment responses, and care coordination, and stepped-care recommendations provided by a psychiatrist. Collaborative care interventions for depression have been evaluated in a wide range of care settings and have been shown to increase quality of patient care and reduce health-care costs.9,10  

SMaRT Oncology-2 Trial

The SMaRT Oncology-2 trial, reviewed in this issue of The ASCO Post, is a randomized controlled effectiveness trial for an integrated collaborative care treatment model for cancer patients with major depression, referred to as “depression care for people with cancer.”1 The study was conducted in three cancer centers in Scotland. All enrolled cancer patients had a predicted survival of  ≥ 12 months estimated by their oncologists. Major depression diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria with an additional requirement to fulfill the diagnostic criteria for at least 4 weeks. The primary outcome was treatment response, defined as a ≥ 50% reduction in Symptom Checklist Depression Scale (SCL-20) score at 24 weeks.  The outcome data were collected up until 48 weeks.

Collaborative care was delivered systematically by a team of oncology nurses and psychiatrists in collaboration with primary care physicians. Usual care was provided by primary care physicians. In the collaborative care intervention, nurses established a therapeutic relationship with the patients, provided information about depression and its treatment, delivered brief evidence-based psychological interventions (namely, problem-solving therapy and behavioral activation), and monitored patients’ progress over a period of 4 months in a maximum number of 10 sessions in person or over the phone. After the initial 4 months, Patient Health Questionnaire (PHQ)-9 depression severity scale scores were monitored monthly by telephone for another 8 months; additional sessions with the nurse were provided for patients not meeting treatment targets.

The psychiatrists supervised treatment on a weekly basis, aiming to achieve and maintain treatment targets, advised primary care physicians about prescribing antidepressants, and provided direct consultations to patients who were not improving.  Of the 500 participants, 253 cancer patients with major depression received the intervention and 247 patients received usual care. About 70% of all patients were 60 years or older and 90% of all participants were women.

More than two-thirds of patients had a history of depressive episodes. Around 50% of all patients had the current depressive episode for longer than 6 months. Seventy-nine percent of patients did not have active disease. Only 13% of patients in the integrated care arm and 16% of patients in the usual-care arm were receiving palliative treatment. The mean SCL-20 depression scores were 2.10 in the intervention group and 2.11 in the usual-care group at baseline.

Sixty-two percent of participants in the collaborative care group and 17% of participants in the usual-care group responded to treatment at 24 weeks. Cancer patients with major depression who received the integrated collaborative care treatment model were found to have less depression, anxiety, pain, and fatigue and better functioning, health, quality of life, and perceived quality of depression care at 24 and 48 weeks (all P < .05).

More than half of the participants in each group received antidepressants. Minimum effective doses of antidepressants were used more commonly in the collaborative care group, and adjustments to antidepressant medications were more frequent. The mean additional cost per patient of providing integrated care was around $1,000. The treatment effects of the collaborative intervention in this study are significantly greater than those observed in similar collaborative intervention trials in cancer patients, in patients with depression comorbid with chronic diseases, and in the general patient population.11-13 

The collaborative care used in SMaRT Oncology-2 included comprehensive depression treatments, namely medications and psychotherapy delivered primarily face-to-face, and intensive education provided to nurses delivering care via formal training and close supervision throughout the study. Involvement of primary care providers increased treatment acceptability and adherence.

It might be difficult to simulate all these treatment components in all oncology care settings. Thus, it might be most valuable to identify which components provide the most benefit. For example, in a randomized controlled trial of collaborative depression care in obstetrics and gynecology clinics, patients with no insurance and patients with public coverage were found to benefit most significantly from this comprehensive approach for management of their depression.14

Referral Critical for Treatment of Depression

One of the important findings of the study is that the primary care physicians and oncologists in the usual-care arm had the option of seeking consultation from a mental health professional for patients with major depression. Although oncologists were informed of a patient’s depression diagnosis, less than 20% of patients were referred to a mental health professional for consultation. More and more cancer centers have robust psycho-oncology programs staffed by psychiatrists, psychologists, social workers, and mental health nurses.

Such programs are now mandated in all National Cancer Institute–designated cancer centers. Further, these programs are critically important and should be increasingly used to aid oncologists in the care of their patients with depression or other forms of psychological distress that often interfere with treatment adherence or completion of treatment. ■

Disclosure: Drs. Breitbart and Alici reported no potential conflicts of interest.


1. Sharpe M, Walker J, Hansen CH, et al: Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): A multicentre randomised controlled effectiveness trial. Lancet 384:1099-1108, 2014.

2. Walker J, Hansen CH, Martin P, et al: Prevalence, associations, and adequacy of treatment of major depression in patients with cancer: A cross-sectional analysis of routinely collected clinical data. Lancet Psychiatry 15:1168-1176, 2014.

3. Mitchell AJ, Chan M, Bhatti H, et al: Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: A meta-analysis of 94 interview-based studies. Lancet Oncol 12:160-174, 2011.

4. Krebber AM, Buffart LM, Kleijn G, et al: Prevalence of depression in cancer patients: A meta-analysis of diagnostic interviews and self-report instruments. Psychooncology 23:121-130, 2013.

5. Wilson KG, Chochinov HM, Skirko MG, et al: Depression and anxiety disorders in palliative cancer care. J Pain Symptom Manage 33:118-129, 2007.

6. Brown LF, Kroenke K, Theobald DE, et al: The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology 19:734-741, 2010.

7. Breitbart W, Rosenfeld B, Pessin H, et al: Depression, hopelessness, and desire for hastened death in terminally ill patients with cancer. JAMA  284: 2907-2911, 2000.

8. American College of Surgeons: Cancer program standards 2012. Available at Accessed September 17, 2014.

9. Huffman JC, Niazi SK, Rundell JR, et al: Essential articles on collaborative care models for the treatment of psychiatric disorders in medical settings: A publication by the Academy of Psychosomatic Medicine Research and Evidence-Based Practice Committee. Psychosomatics 55:109-122, 2014.

10. Green C, Richards DA, Hill JJ, et al: Cost-effectiveness of collaborative care for depression in UK primary care: Economic evaluation of a randomised controlled trial (CADET). PLoS One 9:e104225, 2014.

11. Archer J, Bower P, Gilbody S, et al: Collaborative care for depression and anxiety problems. Cochrane Database Syst Rev 10:CD006525, 2012.

12. Ekers D, Murphy R, Archer J, et al: Nurse-delivered collaborative care for depression and long-term physical conditions: A systematic review and meta-analysis. J Affect Disord 149:14-22, 2013.

13. Strong V, Waters R, Hibberd C, et al: Management of depression for people with cancer (SMaRT Oncology 1): A randomised trial. Lancet 372:40-48, 2008.

14. Katon W, Russo J, Reed SD, et al:  A randomized trial of collaborative depression care in obstetrics and gynecology clinics: Socioeconomic disadvantage and treatment response. Am J Psychiatry. August 26, 2014 (early release online).

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