Impact of Depression or Anxiety on Opioid and Benzodiazepine Use in Hospitalized Hematopoietic Stem Cell Transplantation (HSCT) Recipients
Authors: Iqbal Madiha , Spaulding Aaron C. , Wood Chanel , Ahmed Salman , Jani Prachi , Manochakian Rami , Paulus Aneel , Kharfan-Dabaja Mohamed A , Ayala Ernesto , Ailawadhi Sikander , Chanan-Khan Asher A. , Niazi Shehzad , Sher Taimur 
Published: October 2019

Abstract
INTRODUCTION:
Patients undergoing HSCT are reported to have a high prevalence of depression and anxiety. These comorbid mood disorders have been known to be associated with alteration in pain perception in patients without hematological malignancies. Pharmacological compounds such as opioid and benzodiazepines are frequently used to manage patient symptomology including pain and anxiety. Patients undergoing HSCT are a unique population where the impact of depression and anxiety on opioid and benzodiazepine use has not been well studied.
METHODS:
The study population consisted of patients who underwent HSCT at a single center for a variety of hematological malignancies from 2015-2018. Opioid and benzodiazepine exposure and dosage was defined in a) Patients who were exposed to opioid including those who were previously exposed and those who were exposed during hospitalization for HSCT b) Patients who were neither exposed to opioid previously, nor during the hospitalization for HSCT. Depression and Anxiety was defined as per PHQ-9 and GAD-7 scales prior to hospital admission. Multivariable analysis was performed to identify differences in opioid status, previous benzodiazepine use, transplant type, Karnofsky score, gender, age, race, and marital status with associated Diazepam Equivalent Daily Dosage (DEDD) (Negative Binomial Regression), and Morphine Milligram Equivalent Daily Dosages (MMEDD) (Logistic and Zero Truncated Negative Binomial Regression).
RESULTS:
A total of 275 patients underwent HSCT including autologous and allogeneic from 2015-2018. Anxious or depressed HSCT recipients had an increased incidence of higher DEDD with an IRR of 1.69 (95% CI: 1.15, 2.49) compared to those who were neither depressed nor anxious (Figure 1). However, patients who reported anxiety and depression did not have a different DEDD than those not anxious nor depressed. In addition, patients who were not naïve to benzodiazepine use prior to admission had an increased incidence of a higher DEDD [IRR of 2.23 (95% CI: 1.61, 3.05)]. Patients undergoing autologous stem cell transplant had a decreased incidence of receiving a higher DEDD [IRR of 0.65 (95% CI: 0.47-0.90)]. African American and other populations had a decreased incidence of receiving a higher DEDD [IRR of 0.40 (95% CI: 0.27, 0.59)]. Patients receiving higher MMEDD had a higher DEDD incidence [IRR of 1.01 (95% CI: 1.01, 1.02)].
Patients who were both anxious and depressed had increased odds of receiving an opioid [OR of 3.35 (95% CI: 1.62, 6.94)] compared to patients who were neither depressed nor anxious. However, patients who were either depressed or anxious did not have different odds of receiving an opioid compared to those who were neither depressed nor anxious. Patients undergoing autologous stem cell transplant had reduced odds of receiving an opioid [OR of 0.17 (95% CI: 0.07, 0.40)]. Patients with less than normal Karnofsky performance status (<90 on scale of 1-100) had an increased incidence of receiving a higher MMEDD [IRR of 2.34 (95% CI: 1.07, 5.12)] when modeled by Zero Truncated Negative Binomial Regression.
Finally, HSCT recipients who were both anxious and depressed had reduced odds of being naïve to opioids [OR0.31 (95% CI: 0.15, 0.67)] compared to recipients who were neither depressed nor anxious. New opioid users had reduced odds of receiving a greater MMEDD [OR of 0.98 (95% CI: 0.96, 0.99)] when compared to previous users. In addition, autologous stem cell transplant recipients had reduced odds of receiving greater MMEDD compared to allogeneic transplant recipients (OR 0.33, 95% CI: 0.16, 0.66).
CONCLUSION:
Comorbid depression and /or anxiety impact opioid and benzodiazepine use in patients undergoing HSCT. The presence of these comorbid conditions and their association with increased use of opioids and benzodiazepines can also affect various health related outcomes. Larger studies are needed to fully understand the potential impact of this association on health related outcomes.
Figure 1. Figure 1.

Disclosures
Kharfan-Dabaja: Incyte Corp: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau; Seattle Genetics: Speakers Bureau. Ailawadhi:Amgen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy.