Prevalence of Psychotropic Polypharmacy and Associated Healthcare Resource Utilization during Initial Phase of Care among Adults with Cancer in USA

More than 1.5 million new cases of cancer are diagnosed each year in USA [1] and mental health and adjustment disorders are common among these patients [2, 3]. It is estimated that about 50% of patients diagnosed with cancer experience clinically significant psychosocial distress and mental health disorders that may have a negative impact on their quality of life [2, 4‐6]. The Institute of Medicine considers psychosocial care an essential part of good-quality cancer care and recent treatment guidelines have suggested the integration of psychosocial support and mental health services into the routine care of patients with cancer [7, 8]. Cancer by itself and its treatment may precipitate several cancer-related symptoms such as fatigue, pain, anorexia, sleep disturbances, and cognitive dysfunction [9]. Psychotropic medications are widely used to treat these cancer-related symptoms [10]. As a result, psychotropic medications have become an important tool in a multidisciplinary approach to mental health issues related to cancer care [11]. These medications are often prescribed for both psychiatric and non-psychiatric cancer symptoms [12‐18] by psychiatrists, oncologists, and primary care physicians, especially around the time of diagnosis and initial phase of cancer care (i.e., the first year following cancer diagnosis) [19‐21].

In routine medical practice, psychotropic polypharmacy (PP), the concomitant use of two or more classes of psychotropic medications in one patient, is not uncommon [22]. Although each drug may have an appropriate indication, this practice has received much attention in the last decade because of increased pill burden, increased healthcare cost, and safety concerns related to drug–drug interactions not only between psychotropic medications, but also between psychotropic medications and anticancer medications [23‐27]. Accordingly, the annual direct cost of cancer care in USA is expected to rise from US$104 billion in 2006 to about US$173 billion by 2020 with a corresponding increase in healthcare resource utilization [28, 29]. A few studies have described the use of psychotropic medications in patients with cancer [17‐21, 30‐32] but none have examined the impact of PP on healthcare resource utilization during the initial phase of cancer care when initial courses of cancer treatment including adjuvant therapy are usually expected to be completed. This period of active cancer treatment is characterized by significant psychosocial distress, psychotropic medication use, and frequent clinical encounters. Prior studies have shown healthcare resource utilization and cancer-related costs to vary by several factors including cancer type, stage at diagnosis, sex, and area of residence [33, 34] with the greatest expenditure occurring among those with metastatic cancer, especially during the last year of life [34‐36]. The purpose of the study was to examine the prevalence of PP, and the relationship between PP and healthcare resource utilization during the year following the initial diagnosis of breast, prostate, lung, and colorectal cancers.

Several cancer- or cancer treatment-related symptoms are managed with psychotropic medications [9, 10, 19‐21, 48]. In certain clinical situations, the use of more than one psychotropic medication is appropriate and supported by empirical evidence. For example, the addition of antipsychotics to either antidepressants for the treatment of major depression with psychotic features [49] or to mood stabilizers for the management of acute mania [50] is considered the standard of care. Similarly, the short-term use of benzodiazepines with antidepressants to treat major depression may be clinically justified [51]. Furthermore, patients with treatment-resistant disease may require dual therapy, and for many patients, depression, anxiety, pain, and psychosis may coexist, warranting the use of multiple psychoactive medications.

We examined the prevalence of PP, predictors of the use of PP during the initial phase of cancer care, and the association between the use of PP and healthcare resource utilization. We found that the proportion of patients who received PP increased slightly from the baseline period to the initial phase of cancer care among all patients and for all cancer types included in our study. Prevalence of psychotropic medication use and PP at baseline were relatively low (6.2%), likely because most patients in our cohort did not have any psychiatric conditions during the year leading up to their first cancer diagnosis. A previous study found that the risk of mental health disorders is temporally related to the diagnostic work-up for suspected cancer with a corresponding increased use of psychotropic medications from about a month before a cancer diagnosis that peaks at about 3 months after [52]. This may explain the modest overall increase in the prevalence of PP use from 6.2% at baseline to 7.4% after cancer diagnosis in our study sample.

In this study, we found that in addition to the number of psychiatric conditions at baseline, sex, age at cancer diagnosis, and physical comorbidity at baseline were also significant predictors of the use of PP during the initial phase of cancer diagnosis. Type of cancer was not a significant predictor of PP use during the initial phase of cancer care. This finding is partially similar to that reported in a previous study that showed no significant association between type of cancer and the use of antidepressants [53]. Other studies have found a similarly higher prevalence of psychotropic medication use and PP among women and patients with comorbid conditions [21, 30, 54].

A higher prevalence of PP was observed among patients with lung, colorectal, and breast cancers compared with those with prostate cancer. These findings are consistent with those reported in an analysis of self-reported medication use among survivors of patients with breast, lung, and colorectal cancers [30]. A retrospective cohort study of community-based Medicare beneficiaries also found that patients with prostate cancer were least likely to receive any psychotropic medications compared with patients with breast, lung, and colorectal cancers [55]. One potential reason for a lower prevalence of PP among patients with prostate cancer is that a diagnosis of prostate cancer may be associated with less psychosocial distress requiring pharmacotherapy because a significant portion of patients with prostate cancer die with the disease rather than from the disease.

We found that the use of PP during the first year after a cancer diagnosis was associated with increased rates of outpatient visits, office visits, inpatient admissions, and length of hospital stay after adjusting for certain potential confounding factors. Patients with newly diagnosed cancer often require chemotherapy and concurrent use of multiple psychotropic medications places them at a significantly higher risk of adverse drug–drug interactions that may require additional healthcare services for their effective management [24, 27, 56]. Patients who received PP in our study were more likely to have many chronic physical and psychiatric conditions. This may explain why they experienced more frequent clinical encounters and received more psychotropic medications. To the best of the authors’ knowledge, this is the first study to examine the prevalence and predictors of PP during the first year of cancer care among patients with newly diagnosed breast, prostate, lung, and colorectal cancers in USA using a large insured adult population.

Our study design has some limitations. First, multiclass PP relies on a grouping of psychotropic medications into classes that is based on certain clinical syndromes or mechanisms of action that may not fully capture their pharmacological properties. In recent years, some psychotropic medications have received approvals for multiple indications. Because we did not assess the appropriateness of PP or adverse effects, we do not know if increased healthcare utilization is directly attributable to the consequences of PP or mental healthcare. In addition, some information that may impact on the use of psychotropic medications on healthcare resource utilization was not captured in our data source. Specifically, data on variables such as race/ethnicity, socioeconomic status, clinical information about the cancer (e.g., severity, tumor stage, tumor size, and tumor grade), performance status, and patient preferences and beliefs about alternative treatments was not available in the extant database. Second, a cross-sectional design limits our ability to make causal inferences owing, in part, to lack of temporality. We also conditioned our analysis on survival during the initial phase of care and occurrence of metastatic disease measured after baseline, which could induce selection bias. As a result, the true rates of PP among patients with cancer are likely higher than our estimates because psychotropic medication use often starts during evaluations for suspected cancer and peaks after cancer diagnosis, and may persist during terminal care [21]. Patients who had more advanced cancers and died during the initial phase of care were excluded, which may have resulted in healthier patients included in our analysis, as compared to all patients with incident cancer in the database. The list of procedure codes for office visits may not be exhaustive. Last, the study focused only on a commercially insured population, hence the findings may not be generalizable to other populations.

Patients with PP during the initial phase of cancer care utilized more healthcare resources than those without PP. There was a small but statistically significant increase in the use of psychotropic medications and PP after initial cancer diagnosis, and the proportion of patients receiving PP differed by the type of cancer. Given current treatment guideline recommendations, this increase may be the result of a greater inclusion of a psychiatrist specialized in psycho-oncology in multidisciplinary cancer care teams, and the availability of newer psychotropic medications. Psychotropic medication use may be an indicator of better assessments of psychosocial distress associated with a new cancer diagnosis. These findings emphasize the importance of evidence-based psychotropic prescribing and close surveillance for potential adverse psychotropic drug–drug interactions in patients with cancer, and suggest that patients with cancer with mental health illnesses, even when treated, require a higher degree of healthcare services. Further research is needed to determine the proportion of increased healthcare resource utilization in this population attributable to the underlying mental health co-morbidity, or psychotropic medication side effects, interactions, or other potential adverse outcomes of therapy.