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    wemomvenengees Neuropsychiatric Disease and Treatment ISSN: (Print (Online) Journal homepage: httos//wtandfonline.comiloVéndt20 Anxiety and depression in patients with head and neck cancer: 6-month follow-up study Yi-Shan Wu, Pao-Yen Lin, Chih-Yen Chien, Fu-Min Fang, Nien-Mu Chiu, Chi-Fa Hung, Yu Lee & Mian-Yoon Chong To cite this article: Vi-Shan Wu, Pao-Yen Lin, Chih-Yen Chien, Fu-Min Fang, Nien-Mu Chiu, Chi- Fa Hung, Yu Lee & Mian-Yoon Chong (2016) Anxiety and depression in patients with head and neck cancer: 6-month follow-up study, Neuropsychiatric Disease and Treatment, , 1029-1036, DOt: 10,2147/NDT.S103203 To link to this article: https://dol,org/10.2147/NDT.S103203 © 2016 Ww etal. This work is published and licensed by Dove Medical Press Limited BB puviisned ontine: 27 apr 2016. CF submicyour article to thisjournal [ail rece views 212 LEG view cotton articles C7 @® View crossmark data CB) citing artces: 23 View citing articles Full Terms & Conditions of access and use can be found at hutpsy/wmwtandfonline.com/action/journalinformation2journalCade=dndt20 Neuropsychiatric Disease and Treatment Dove; 3a ORIGINAL RESEARCH Anxiety and depression in patients with head and neck cancer: 6-month follow-up study Yi-Shan Wu! Pao-Yen Lin'? Chih-Yen Chien? Fu-Min Fang‘ Nien-Mu Chiu! Chi-Fa Hung! Yu Lee! Mian-Yoon Chong! "Department of Paychitry,nsueute {for Translational Research in Biomecieal Sciences, “Department of Otolaryngology. “Depariment of Radiation Oncology Kachsiung Chang Gung Memorial Hospital, Chang Gung University Collegeof Medicine Kaohsiung, Talwan Correspondence: Mlan-Yoon Chong: Department of Poyhity, Kachsing (Chang Gung Memorial Hosp 123 TaPel Rous, NsosSung, Kaohsiung 833, Taiwan “Tel 18667 7317123 ox 67536318 Fr + 686 7732 6817, Email mchong@egmhorgsw: hur2@eanhorgsw Objective: We aimed to assess psychiatic morbidities of patients with head and neck eancer GINC) in a prospective study at pretreatment, and 3 and 6 months after treatment, and to compare their health-related quality of life (IRQL) between those with and without depressive disorders (depression) Materials and methods: Patients with newly diagnosed HNC from a tertiary hospital were recruited into the shady. They were assessed for psychiatric morbidities using the Structured Clinical Interview for the Diagnostic and Staitical Manual of Mental Disorders, fourth ciltion. Their HRQL was simultaneously evaluated using the quality of life questionnaire of the Bucopean Organisation for Research and Treatment of Cancer with a specific mode for head and neck cancer; and depressed and nondepreseed LINC patients were compated by using the generalized mixed-effect model for repeated measurements Results: A total of 106 patients were seerited into this study. igh rates of anxiety were {ound at preweatment, but steadily declined overtime (feom 27.3% fo 6.4%, and later 3.3%), AA skew pattem of depression was observed, with prevalence rates from 8.5% at pretreatment 024.5% and 14% at 3 and 6 months, respectively, afler treatment. We found (P-0.001), loss of speech (P<0.001), low libido (P-0.001), dry mouth (P<0.001), and weight loss (P=0.001) were related to depression aver time. The depressed patient had a higher con- sumption of painkillers (P=0.001) and nutrition supplements (P=<0.001), The results showed that depeession was predicted by sichy saliva (P=<0.001) and touble with social contaet (P<0,001) at 3 months, and trouble with social eating (P<0,001) at 6 months. Conclusion: Pationts with HINC experienced different changes in anxiety and depression in the fist 6 months of treatment. Dysfunction in salivaton, problems with eating, and problems ‘with social contacts were major risk factors for depression Keywords: depression, anxiety, quality of life bat loss of sense Introduction Patients with head and neck cancer (HINC) may suffer variable degrees of functional impairment that a ‘well as facial disfigurement during treatment and in the illness course. They are at higher risk of having emotional distress than any other form of cancer amid loss of these functions '? Emotional disorders might be expected after a diagnosis of cancer and going through a period of enduring adaptation tothe illness from weeks to months. ‘Understanding the time course forthe impairment ofthese functions to affect the mood is important for the commencement of early intervention. ‘Areview ofthe literature revealed that there was wide variation in reported rate of depression in patients with HNC: from 6% to 48%,’ However, this huge discrepancy ly because of differences in 1) method of investigation, 2) measurement, ‘elated to speaking, swallowing, breathing, taste, and smell, as ‘Neuropsychiatric Disease and Treatment 201612 1029-1036 1029 TT ce an pag 21a rd Weel 3) samples, 4) degree of severity or staging of the cancer, and 5) time points of assessment. In general, higher rates of depression were estimated when using patient self-reported ‘questionnaizes, where overrating might be seen in most items ‘of somatic dysfunction, particularly patients suffering from chronic or acute physical illness.*Krebber etal" conducted a ‘meta-analysis, and found that the average rate of depression in HNC patients was 20% when measured by self-reported ‘questionnaires, but only approximately half of that (11%) when a diagnostic interview was employed. Most of these studies were done with patients at 1 year ‘of later, and there have not been many studies on psychi- atric morbidity of HINC patients during the early phase of treatment.” Following the illness course and treatment, the quality of life (QL) of cancer patients is expected to be affected with the loss of physical and health-related functions. Using a standardized structured interview and validated instrument for the assessment of QL, this study followed patients with newly diagnosed HINC, to 1) assess psychiatric morbidity and its changes, specifically with anxiety and depressive disorders (depression) at pretreat ‘ment, 3 months, and 6 months; 2) assess the health-related QL (HRQL) of the patients with HNC; and 3) identify risk. factors for depression with various health-related function losses that are associated with HNC. Materials and methods Subjects This was a prospective study of newly diagnosed HINC patients atending the outpatient combined-eatment clinic for INC at Kaohsiung Chang Gung Memorial Hospital in southem Taiwan between January 2011 and January 2012. The inclusion criteria were newly diagnosed and untreated INC notmetastatic cancer, andhaving the ability to verbalize and wit, Patients witha istry of recurrent HNC or previous malignancy wete excluded, In addition, patients with demen- tia and delirium were also exchded from this study Procedures ‘This study was approved by the Human Research Ethics Committee of Chang Gung Memorial Hospital (98-3563B), All patients retumed written consent before they were included in the study. The psychiatric interview was carried ‘out by a research psychiatrist, while the social and demo- ‘graphic information, as well as QL, was also simultaneously collected by a trained research assistant, The patients were prospectively followed and assessed for their psychiatric ‘morbidities and HRQL. before treatment (pretreatment) and at 3 and 6 monte. Structured Clinical Interview for DSM-IV, clinician ver Psychiatric morbidity were being assessed and made using ‘the Structured Clinical Interview for the Diagnostic and ‘Statistical Manual of Mental Disorders (DSM)-IV (SCID), clinician version, a structured diagnostic interview based oa DSM-IV criteria" The SCID is a clinician-administered, semistructured interview for use with psychiatrie patients or ‘with community subjects who are undergoing evaluation possible psychiatric diseases. Its main framework consists of nine diagnostic modules. Interviewers may choose to climinate one or more modules to focus selectively on areas of the greatest diagnostic interest. Most sections start with a leading question that allows the interviewer to “skip” the subsequent questions ifnot met. The SCID is regarded as a gold standard for psychiatric diagnosis, and it was conducted by a senior psychiatr and research experience (YL) with over 25 years of clinical Assessment of health-related quality of life ‘The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) was used to assess QL. for cancer patients. It has been translated and validated into 81 languages. Various modules have been developed for disease-specific treatment measurements, and in this study we used the module that is specific to the HINC (the QLQ — Head and Neck [H&NJ-35)? This consists of 35 questions on a4-point scale (1=not at all, 4= very much), ‘with seven multiple items on pain, swallowing, senses (taste and smell) speech, social eating, social contact, and. sexuality, and eleven single items on other health functions related to teeth, mouth opening, dry mouth, sticky saliva, cough, feeling ill, painkillers, nutition supplements, feed- ing tube, weight loss, and weight gain, Al scales ranged in a transformed score of 0-100. A high score on a symptom, scale or single item indicates more severe symptoms oF problems. It has been validated using Taiwanese samples with good test-setest reliability and internal consistency." The EORTC QLQ-H&N35 has been widely used f studying HRQL. in HINC patients in Taiwan and European, countries. Statistical analyses The demographic characteristics, peychiatrc diagnoses, his- tory of substance use (alcohol, smoking, betelnut, clinical staging of cancer, and treatment methods and HRQL were frst summarized using descriptive statistics. They were then compared between patients with and without depression using 7 or tests. 1030 ‘Nesropaycharc Disease and Tanto 201677 Dove) Arty and dpresion In HNC With items based on the EORTC QLQ-H&N3S, HRQL was analyzed and compared across time using analysis of ‘variance for repeated measurements, To investigate the effect of depression at each time point on HRQL, a generalized mixed-effect model for repeated measurements was used This has the advantages over traditional methods, such as last observation carried forward, of including all available ata across the follow-up period and providing better esti- ‘mates under a broad assumption of missing data, Bach item of the EORTC QLQ-H&N3S at pretreatment and 3- and Gemonth assessment was explored as the primary outcome, with depression at each time point used as the dependent variable, Post hoc estimation was also applied to compare outcome variables among these three time points, To avoid false positives, Bonferroni correction was used to correct exrors made in the multiple testing procedures. Results Characteristics of samples Of the 106 patients who were recruited in the study, 93 sue- cessfully completed the study. Among those who did not complete the study, three died and ten were uwiling to continue during the followup period and excluded. Table 1 shows the sociodemographic and clinical characteristics of ‘the patients, with the majority being males (86%) and an average age of 52.729.6 yeas. Three-quarters of them were married and currently employed, and their mean educational level was 9.943.7 years. Substance use was commonly seen in these patients, with 63.4% smoking, 41.9% drinking alcohol, and 29% betel-nut chewing. Approximately two-thirds ofthe patients were diagnosed as having advanced clinical stages of cancer (Ill and IV), and over half received surgical and/or chemo- and radiotherapy. The time to initial treatment after the diagnosis was 2.2+1 4 weeks (Table 1) Psychiatric morbidity ‘Atte prereament evaluation, more than half had one or tore psychiatric diagnoses. Because ofthe stall number of Patients, we grouped the diagnoses of “adjustment disorder with anxious mood” and “anxiety disorder not otherwise specified” ino anxiety disorders (anxiety), andl deprestve- spectrum disorders into depressive disorders (depression). The prevalence of paychiatic disorders after the regroup- ing was as follows: anxicty disorders (27.3%) disorder (18.9%), depressive disorders (8.5%), and insomnia (2.8%). Diuring the G-month period, there were some changes in the distribution of paychiatrc morbidities, wth the most significant being the consistently and sharply decreasing | aleoholause imaty Table I Sociodemographic and clinical characteristics of head and neck cancer patients Yan a Sex le 80 86 Female B 4 ‘Age, years =40 8 86 41-59 6 088 60 2 ne Education, years Mean 48D 9917 <6 27 » rR sé oo2 SB i 108 Marital status Unmarried u 258 ried 6 m2 Unemployed 8 269 Substance used AAcohol 38 ais Tobacco 9 os Bese nt a » Week after dlagnosis, mean SD 22114 Cancer staging Early (age HI) 3 aS ‘Advanced (sage ILM) © os Treatment received Surgery only 2 a7 cemTiccRT a 462 Surgery + CCIRTICCRT. 2 2 rate of anxiety disorders (from 27.3% to 6.4% and 3.3% at pretreatment and 3 and 6 months, respectively). There was not much change in alcohol-use disorders, with rates ranging 1m 18.9% to 20.4%. Depression showed a skew pattern, with a rise in the rate after pretreatment (8.5% times that at the peak at 3 months (24.5%), but gradually receded neatly to the level of initial assessment at 6 months (Figure 1). Psychiatric morbidity with any psychiatric agnosis declined steadily during the 6-month period (with rates from 54.7% at pretreatment to 45.8% at 3 months and 38.7% at 6 months), to three Six-month HRQL ‘The 6-month follow-up of HRQL, with results from the assessment on items based on the EORTC QLQ-H&N35 at pretreatment, 3 months, and 6 months is shown in Table 2 Allexcept the use of feeding tubes were significant over time, with some differences in patterns of distribution. Similar to the pattern of the rate of depression, patients felt worse and ‘had more pain and higher frequency of taking painkillers in FNeoropaychinerc Disease and Tranoment 70167 Tost Doves Wise —E Depression Annisly = Acohor 30 23% 5% 2 204 ap 189% * 213% R15 10% 10 am 5 84 % aK Proreaiment 3 monthe ‘months Figure | Pcie mort oad and eck cer ens ret tena the first 3 months. Levels returned to approximately the level of pretreatment at 6 months, together with dysfunction of ‘mouth opening, swallowing, sticky saliva, sense and speech problems, trouble with social eating and social contact, and ‘weight loss. The problem with teeth varied over time, but coughing and sexual function decreased with time, Dry mouth persistently increased during the 6-month period, despite a small but steady increment of weight gain ‘Table 2 Hesle-related quality of Me, with items from the EORTC QLQ-HAN3S at pretreatment, 3 months, and 6 months heb months Povalve Pan sa 3 01° Swallowing 52 18 0001" Sense problem 22 22 36 0001" Speech problem 3.4 50 ar 01 Troublewicn 54 86 72 <0001* social etng Troublewitn 60 1a 66 oor social contact Senuliy bs 30 33 002% Teeth as 4 W 008s Openingmowth 18 24 9 0012 Drymouth 17 24 28 <0001* Sedky salva 16 26 2 <0001* Coughing 24 le a 0008 Fete i WW 21 12 0.005" Pain les 13 Is uu 0012 Nuttin 17 W Is 0001" supplement Feetingtube 15S 2 to oan Weigiclos 13 ls uu <0001* Weighe in 1.0 12 1B 00. Cancer QLHEN, Quay ole Questonnire Hand nd Neck Depression and HRQL When comparisons were made between the depressed and nondepressed HNC patients, there were no significant dif ferences in their sociodemographics (sex, age, marital sta- tus, employment, education, and substance us) or elinical characteristics (cancer staging, time to initial treatment, and mode of treatment) (Table 3) Despite significant changes in HRQL on almost all items of the EORTC QLQ-1&N35 during the 6-month period, there were some diferences between the two groups across time when they were analyzed further using the generalized mmixed-effect model. The results showed that overtime, Joss of functions to sense (P<0.001), speech (P<0.001), sexuality (P<0.001), and dry mouth (P<0.001) were only significantly elated to depression, and those with depression hada higher tendency to take painkillers (P<0.001) and ‘nutrition supplements (P<0.001) than nondepressed patents ‘However, depression was predicted by sticky saliva and problems with social contact at 3 months and socal eating at 6 months (Table 4). Discussion This prospective study showed that patients with HNC suffered from variable degrees of psychiatric morbidities during the first 6 months of treatment course. More than a quarter had an anxiety disorder (27.3%) at pretreatment, but the rate steadily declined to 3.3% during the 6-month period. Depressive disorder, however, did not follow such a pattern, >but changed over time and manifested a skew pattern, with arise in rate during the first 3 months (from 8.1% to 24.5%) and then a gradually return to pretreatment level in later months (14%). ‘When patients were first confronted with the diagnosis of HINC, anticipatory anxiety was commonly seen, along with symptoms of overwhelming information, distractibility, and poor sleep. At this phase, a high rate of anxiety was demonstrated, similar to previous research." However, once the patients were more adapted to the disease and with the progress of treatment, the rate of anxiety significantly declined." Early intervention by the team, which included psychiatrists and psychologists, also helped reduce tension and anxiety of the patients. We used a standardized structured interview in the assess- ment of psychiatric symptoms and diagnosis (SCID) instead of a self-reported questionnaire. Such a procedure could avoid erroneous rating of symptoms of HNC for depression oF because of the adverse effects of the treatment. For example, physical symptoms with appetite and body-weight loss are common in cancer or during the treatment process. It is thus 1032 ‘Nesropaycharc Disease and Tenement 701672 Dove) Arty and dpresion In HNC Table 3 Comparisons of sociodemographic and clinical characterises between head and neck patents with and without depression Varabies Depressed, n GO) Nondepressedsn (@) Pieter Prvalue Sex Mae 14s) 63) ons 1 Fesnale 2154) 137) ‘Age, years Mean #5 5.196 s1ass6 06! 0339 40 Van 788) 4159 loss) 54674) 005 om 60 2154) 19238) Education, years Mean =5D aes loss 1207 o23i <6 4008) 288) ra 8618) 4860) os os > lan 94112) Marital status Unmarried 4.008) 29.5) 0194 ons Married 9 (692) os) Unemployed 4008) 21 63) ons oven Substance ured Alconel 6462) m0) ours ors Tobacco o7s9) 49 (613) Lise 0361 Bete nut 4008) 2228) oo 1 Weeks ater diagns Lett 234 11 oa Cancer staging Ely age HD) 2454) 31 988) 2087 our ‘Acsaneed (age IM) 11646) #9613) Treatment received Surgery only 2s) 21 962) 0997 ene ccRTiCcRT (462) 37 (463) Surgery + CCIRTICCRT 584) n2075) ‘Table 4 Comparison of health-relted qualty of life between depressed and nondepressed head and neck cancer patents items &) an (SD) ‘months, mean (SD) ‘Depreston, Nondeprested, Nondeprested, Depressed, Nondeprensed, Pvalue Prvalue 97 nT nid n-80 rin 52@2)_ S4(17) 71@8) 625) @203) 46013) Swilowing —S4G1) 52) 2904 7404 sre) 6108) Sense problem 26(1I) 21 (07) 4709) 41) 39@) 350) 000! Speech problem 46@) 3309) 6403) 4508) 6908) 4408) <0001 Troulewih 704) $203) sel) 7304 ie) — 66@2) 0001 (6 socal eating Troulewt — 8386) 5818) 9904 653) nae sean) -<0001 0) socal contact Senulty l7e9) M2) 4a) 26) 570) 29019) oo! Teeth 3322 23@) let.) 13@7) 23) (hh Opening mouth 2113) 18) aay 2d) ascii) 18h) Drymouth 147) 17(LI) aii) -22(h) 32(13) 27013) Sticky va 26) 1508) 34qi2) 24413) 2a(l3) 24413) <0001 0) Courhing LAC) 2508) 16@8) 1608) 1s) 1205) Fete 203) 7) 30) 180) 2701) 1608) Pikes 16) 13 8) lees) 1504) 1405) 143) ot Navin —-26(12) 1707) 18@4) 175) 1705) 155) 0001 sepplement Feedingtsbe 165) 15 (05) 1204) 12@4 hea) 12) Wernloss 165) 1308) 1804) 16 @5) 14005) 1.43) Weeteain 1103) 1) 113) 12@4) 1103) 13.@3) co! earopychite Dae and Tan ee 1033 Weel Doves important to differentiate symptoms of “losing of the function to eat (a symptom of HNC)” with “losing of the desire to eat (asymptom of depression)”, where both will eventually result, inthe loss of body weight. Most self-reported instruments of depressive symptoms nevertheless are not able tomake such distinctive differences.‘ Also, since the SCID assessment was conducted consistently by only one rater, there was less ‘concer about the problem of interrater reliability. To further assess various symptoms and that were related to the cancer, we employed a question- naire on HRQL with a module that is specific for HNC: the EORTC QLQ-HANSS, It was found that there was signifi- ‘cant impairment in all items of HRQL during the 6-month period of treatment, except with the use feeding tubes (Table 3), Some of these symptoms might have correlated ‘with depression, and this was able to be identified by applying analysis using the generalized mixed-effeet model {for repeated measurements across time. The results showed that the HINC patients with depression had more significant impairment than nondepressed patients in problems with sense and speech, dry mouth, sexuality, and loss of weight. ‘The depressed patients had higher consumption of mutri- tional supplements and painkillers. The use of painkillers, ‘especially those with narcotic analgesics, has been reported to have a higher risk of depression." ‘The rates of depression in this sample of HNC patients ranging from 8% to 25% are compatible with easier studies of longer duration. We found that there were no sig- nificant differences in sociodemographies (sex, age, marital status, employment, education, and substance use) or clinical characteristics (cancer staging, time to initial treatment, and ‘mode of treatment) between patients with and without depres- sive disorders, which might indicate that those factors were not the major cause of depression of HNC patients during the ‘eatment course, Inthe first 3 months of treatment, depres- sion was significantly predicated inpatients with dysfunction in salivation with sticky saliva and trouble with social contact. Dry mouth with sticky saliva is regarded as an adverse sign in Chinese medical philosophy that reflects an imbalance of the internal organ systems:* This might have created pes- simism in these patients if they had dysfunction in salivation and limitation in the ingestion and chewing of food. As food and eating ate intrinsic factors of life and Chinese culture, the loss of such functions among these patients further added to negative thoughts about their vitality and survival. This ‘may partly explain the increasing rate of depressive disorders in the frst few months of treatment, together with the fear lover the uncertainty of their disease course or even death With treatment progress, trouble with social eating was still the main factor related to depression atthe 6-month interval This illustrated the importance of food, eating, and nutrition for these patients, despite impairment of certain physical functions that were related to HINC A fifth of the patients abused alcohol, and this rate was consistent throughout the 6-month period. Although alcohol has been regarded as one of the risk factors for HNC.* the tate of alcohol abuse in this study was considered much lower than most reported studies, of 30%-90%."* Taiwanese generally have a lower rate of alcoholism than Caucasians, due to a lack of related genes for enzymes that are respon- sible for metabolizing alcohol and acetaldehyde, * and this could well have accounted for the relatively low prevalence rate of alcoholism in study. In spite ofthis, ~30% of these patients had the habit of chewing betel nut. Although it ig not related (o any mood disorders, chewing betel nut is however carcinogenic to humans, and has been reported Berel nut to have association with oral/buceal cancer contains a substance called arecoline, which has proved to contribute to histologic changes in the oral mucosa, Aside from betel-nut habits, it is noteworthy that >60% of the patients also smoked, This was not related to mood disor- ders, but might have harmful effects on health and thus to the disease prognosis." is believed that one in four terminally il patients have symptoms of depression, but that up to 80% of this depres- sion may not be recognized and is thus untreated” Among the symptoms, loss of sexuality, appetite, body weight, and sleep are also core vegetative symptoms of depression. In our society and across this region, sexual fanetion has often been disregarded, and is regrettably not routinely inquired about or assessed, The awareness of depression, the identification of symptoms, and the initiation of treatment are essential if patients are tobe offered optimum palliation of psychological as well as physical symptoms. Conclusion In summary, this study of a 6-month experience of patients ‘with HINC showed that psychiatric morbidities were com- ‘monly seen in the early phase of treatment, High rates of anxiety were found before treatment, but had a steadily decline following the treatment course. Depression, on the other hand, demonstrated a skew patter, with a peak at 3 months declining to pretweatment level at later months. ‘Dysfunction in salivation and problems with social contacts and eating were the three major risk factors for depression at 3 and 6 months, as impairments of sense, speech, dry 1034 ‘Nesropaycharc Disear and Tanto 201672 Dove) Arty and pression In HNC ‘mouth, and sexuality were more significant inthe depressed patients who also consumed more painkillers and nutritional supplements ‘There are some limitations in ths study. First, the sample size was relatively small, and further inferences cannot be ‘made based on the exact anatomical sites that are related to different side effects from treatment (eg, eating and swallowing). Although small in number, patients could be ‘well studied with a prospective design. Second, there was no random selection; a consecutive sampling method was used instead, andit included al cases that fitted the criteria, Third, the follow-up period was relatively short. A longer period is needed to prove the long-term outcome ofthese functions in relation to depression, Acknowledgments This stady was supported bya grant from Kaohsiung Chang Gung Memorial Hospital, Taiwan (CMRPGS91321). The authors thank all patients and their famities who were involved inthe stay, Disclosure The authors report no conflicts of interest in this work, References 1. Abn MH, Pak, Lee HS tal. Suicide i cancer patients within the frst year of agnosis: Pychooncology: 2015:24(3)'01-607 2. 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