Anxiety and depression mediate the association between chemotherapy‐induced peripheral neuropathy and fatigue: Results from the population‐based PROFILES registry

Abstract

Objective Chemotherapy‐induced sensory peripheral neuropathy (CIPN) is common among colorectal cancer (CRC) survivors. The aim of this study was to examine whether CIPN is associated with both psychological distress (ie, anxiety and depression) and fatigue and whether the relationship between CIPN and fatigue can (partly) be explained by psychological distress. Methods All CRC survivors diagnosed between 2000 and 2009 as registered by the population‐based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy‐treated survivors completed questions on CIPN (EORTC QLQ‐CIPN20), psychological distress (HADS), and fatigue (FAS) on average 5.6 years after diagnosis. Simple and multiple mediation analyses were performed to examine anxiety and depression as possible mediators in the association between CIPN and fatigue. Results Survivors with high (ie, upper 30% of scores) CIPN (n = 172) reported more anxiety and depressive symptoms and more fatigue compared with those with low CIPN (n = 299). Furthermore, among survivors with high CIPN, those who were anxious, depressed, or both reported more fatigue compared with those without psychological distress. These differences were clinically relevant. Finally, mediation analyses showed that while CIPN was directly associated with fatigue, the relationship between CIPN and fatigue was also significantly mediated by both anxiety and depression. Conclusions CRC survivors with high CIPN report more fatigue, especially those who are also anxious and/or depressed. More research is needed on the direction of the relationship between CIPN, psychological distress, and fatigue. For now, the treatment of fatigue should also focus on addressing psychological distress, as treating fatigue alone might not be sufficient.

Painful and non-painful chemotherapy-induced peripheral neuropathy and quality of life in colorectal cancer survivors: results from the population-based PROFILES registry

“…The finding that osteoarthritis was a significant correlate is most likely because pain, numbness, and tingling are also frequently reported symptoms in that condition. Regarding anxiety, several other studies also found an association between anxiety and CIPN [12,[22][23][24][25]. As the current study is cross-sectional, we cannot draw conclusions on the direction of this association.…”

Long-Term Prevalence of Sensory Chemotherapy-Induced Peripheral Neuropathy for 5 Years after Adjuvant FOLFOX Chemotherapy to Treat Colorectal Cancer: A Multicenter Cross-Sectional Study

“…As expected, the CIPN had a strong impact on anxiety, depression, fatigue, and HRQoL (physical, role, and emotional functioning) [ 30 , 44 ]. Sensory CIPN has been associated with depression and sleep disturbances [ 45 ].…”

Post-surgery anxiety and depression in prostate cancer patients: prevalence, longitudinal progression, and their correlations with survival profiles during a 3-year follow-up

“…Another study reveals that depression correlates with worse clinical outcome in gastric cancer patients, and the in vivo and in vitro experiments disclose that gastric cancer-related depression involves the participation of reactive oxygen species via the ABL1-modulated inflammatory pathway [25]. In addition, a previous study illustrates that anxiety and depression play a role in mediating the correlation of chemotherapy-induced peripheral neuropathy with fatigue in colorectal cancer patients; however, this study also states that this needs more experimental evidence to validate [26]. Furthermore, there are already findings regarding cellular mechanisms of the harmful impact of anxiety and depression on prostate cancer patients.…”

“…Second, anxiety and depression also induce many physical symptoms, such as fatigue, insomnia, and change of weight as well as appetite; these all contribute to a worse physical function and may interfere with the physical health of prostate cancer patients [31,32]. Third, anxiety and depression may aggregate the disease in prostate cancer patients via affecting several biological processes or pathways, such as regulating the tumor infiltrating NK cells and reactive oxygen species [24][25][26][27]. In the future, the status of anxiety and depression may be useful in optimizing the prognosis prediction in surgical prostate cancer patients; however, this should be validated by more highquality trials or large-scale cohort studies.…”