PERSISTENT POSTTREATMENT DEPRESSIVE SYMPTOMS IN PATIENTS WITH HEAD AND NECK CANCER

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1 ORIGINAL ARTICLE PERSISTENT POSTTREATMENT DEPRESSIVE SYMPTOMS IN PATIENTS WITH HEAD AND NECK CANCER Lucy Hynds Karnell, PhD, 1 Gerry F. Funk, MD, 1 Alan J. Christensen, PhD, 2 Eben L. Rosenthal, MD, 3 J. Scott Magnuson, MD 3 1 Department of Otolaryngology Head and Neck Surgery, Rm PFP, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, Iowa lucy-karnell@uiowa.edu 2 Department of Psychology, University of Iowa, Iowa City, Iowa 3 Division of Otolaryngology Head and Neck Surgery, University of Alabama, Birmingham, College of Medicine, Birmingham, Alabama Accepted 12 September 2005 Published online 30 November 2005 in Wiley InterScience ( DOI: /hed Abstract: Background. This study examined the prevalence and risk factors of persistent (versus short-term) depressive symptoms in patients with head and neck cancer. Methods. Patients with 10þ and 18þ posttreatment Beck Depression Inventory scores for 6 or more months during their first year were identified. Regression analyses determined risk factors associated with persistently high scores. Results. Of the 148 patients, 25.0% and 7.4% were persistently above the 10þ and 18þ cutoff scores, respectively (compared with 33.6% to 44.2% and 9.2% to 18.6% when measured at single points across this time period.) The strongest predictor of persistent posttreatment depressive symptoms was pretreatment depressive symptoms. Conclusions. The percentage of patients with persistently high levels of depressive symptoms, although considerable, is substantially lower when patients with transient mood disorders are omitted. A screening tool that determines high levels of pretreatment depressive symptoms could identify patients at high risk of experiencing posttreatment depression who would be Correspondence to: Gerry F. Funk Presented at the Sixth International Conference on Head and Neck Cancer, August 2004, Washington, DC. Contract grant sponsor: This work was supported by NIH grant R01 CA through the Office of Cancer Survivorship. VC 2005 Wiley Periodicals, Inc. good candidates for clinical intervention. VC 2005 Wiley Periodicals, Inc. Head Neck 28: , 2006 Keywords: depression; head and neck cancer; depressive symptoms; outcomes; longitudinal Depression is frequently associated with cancer, occurring in almost 20% of oncologic patients, according to a study by Zabora et al 1 that examined 4496 people with various malignancies. The site-specific results of this 2001 study indicated that head and neck cancer was among the six types of cancer with the highest mean score for depression when measured within 90 days of diagnosis. Although depression is prevalent among patients with head and neck cancer and is considered a treatable problem, 2 it has not received much attention in the clinical setting. A comprehensive review of current literature indicates that the proportion of patients with head and neck cancer who have mild to severe levels of depressive symptoms ranges from 16% to 44% when measured at a single point in time This large range is primarily due to the different meth- Depression in Head and Neck Cancer HEAD & NECK DOI /hed May

2 ods used to quantify depressive symptoms, including the use of (1) different surveys or cutoff scores within the same survey; (2) different points in time in which measurements are made (from before treatment to a decade after treatment); and (3) different subsets of patients with head and neck cancer (chosen on the basis of site, stage, and type of treatment). Numerous studies have investigated the association between various demographic or clinical variables and high levels of psychological distress measured at single points in time. Several studies have failed to show any link between posttreatment symptoms of depression and age or sex. 5,12 Although one study suggested that marital status was a correlate of depressed mood, 13 another study found no relationship between marital status and level of depressive symptoms. 5 Alcohol use and depression are known to be significantly associated in other patient populations, 14 but two studies in patients with head and neck cancer indicated weak associations. 3,4 The authors of one of these studies concluded that mood disorders in patients with head and neck cancer were not the result of alcohol abuse. 3 Conflicting results have been published concerning the relationship between stage of disease and depression. Two studies indicated no significant relationship between stage and pretreatment 3 or posttreatment levels of depressive symptoms, 6 whereas a third study indicated that advanced disease was associated with a depressed mood. 13 More compelling are the results of investigations that indicated posttreatment depression is related to head and neck cancer specific healthrelated quality of life (HRQOL) and to the existence of depression before treatment. Studies designed to identify pretreatment risk factors found that the strongest predictor of a posttreatment mood disorder was a mood disorder at the time of diagnosis. 6,9 The results of investigations that examined posttreatment variables found that posttreatment depressive symptoms were most strongly associated with concurrent head and neck cancer specific HRQOL outcomes. 5,10,12 Two studies that assessed both pretreatment and posttreatment factors also found posttreatment head and neck cancer specific outcomes to be associated with posttreatment depressive symptoms. In a 1997 study of patients 1 to 4 years after radiation therapy, a significant, but weak, association was found between posttreatment depression and head and neck cancer related performance related to diet and eating in public. 4 Although history of depression was listed as one of the variables included in the univariate analyses, no association between pretreatment and posttreatment depression was cited. A later study in 2000 used a multivariate analysis to determine what pretreatment and posttreatment factors were associated with depressive symptoms up to 1 year after treatment. 15 The results of this study showed that the strongest predictor of posttreatment depression was concurrent, cancer-related health symptoms, and the second strongest predictor was pretreatment levels of depressive symptoms. Last, univariate analyses have shown that time from last treatment is associated with levels of depressive symptoms. 5,6,16 This result, which indicated fewer depressed symptoms as time from treatment increased, highlights how the number of patients identified as being depressed can be influenced by the particular point in time that measurements are made. In all of these studies, the identification of patients with high levels of depressive symptoms was done at isolated points in time. This method was used not only in cross-sectional studies (which measured one single point in time) but also in prospective studies (which measured several single points in time, comparable to a compilation of several cross-sectional studies). Consequently, each study s group of patients with high levels of depressive symptoms contained individuals with persistent depressive symptoms, as well as individuals with acute symptoms that resolved within a relatively short period of time. The authors of several prospective studies alluded to this fact when they reported that the group of depressed patients at each of the different points in time represented a different subset of individuals as new cases cropped up and old cases resolved. 6,9 Clinical intervention directed at alleviating depressive symptoms could greatly improve patients HRQOL. To be efficient and effective, such therapy needs to be targeted at patients who are most likely to benefit. That group of patients should not include individuals with short-term depressive symptoms who are experiencing a mild, dysphoric adjustment reaction to their cancer and its treatment, which reconciles in a relatively short time. Duration of stress, cited by Kendall et al 17 as a necessary component in diagnosing mood disorders, has been shown to correlate with clinical severity. 18 Including a given duration as one of the criteria for identifying the best candi- 454 Depression in Head and Neck Cancer HEAD & NECK DOI /hed May 2006

3 dates for clinical intervention would reduce the number of false-positive results by eliminating many of the borderline/mild cases with short-lived symptoms. The goals of this study were to determine (1) the prevalence of persistent depressive symptoms within the first year after diagnosis of head and neck cancer, which represents those patients who would benefit most from clinical intervention; and (2) factors associated with these protracted symptoms of depression that could be used to identify patients at high risk. If persistently high levels of depressive symptoms are primarily associated with performance status in this patient population, the best method for alleviating depression in the short run would be to identify individuals most likely to have poor HRQOL outcomes. In the long run, it would be helpful to find optimal treatments that result in the best head and neck cancer specific HRQOL. However, if persistently high levels of depressive symptoms are primarily associated with pretreatment levels of depressive symptoms, attempts to alleviate depression would focus on screening for patients who present with a depressive mood disorder and offering them appropriate intervention. MATERIALS AND METHODS This study included patients with carcinomas of the upper aerodigestive tract who completed a survey about their depressive symptoms while enrolled in the University of Iowa Hospitals and Clinics Department of Otolaryngology Head and Neck Surgery s Outcomes Assessment Study. Approximately 75% of all eligible patients are enrolled in this longitudinal study. Surveys are administered to participants during routine clinic visits before treatment and then at 3, 6, 9, and 12 months after their diagnosis. An instrument measuring depressive symptoms was included in the battery of surveys that was administered between February 1998 and November 1999 and then between December 2001 and November (The battery of surveys used in this longitudinal project has undergone several changes over time, and between December 1999 and November 2001, depressive symptoms were not included in the assessment.) Depressive symptoms were assessed using the Beck Depression Inventory (BDI), a 21-item survey with ordinal responses (0 3) that result in a total score ranging from 0 to The BDI is a standardized instrument that has been frequently used to evaluate numerous signs and symptoms of this syndrome. 17 A recent study by Katz et al 11 that compared BDI scores with the findings of a diagnostic interview based on Research Diagnostic Criteria found the BDI to be highly accurate in identifying patients with clinically significant depression within a group of patients receiving radiation therapy for their head and neck cancer. Another finding of the Katz et al study 11 addressed the issue of the BDIs containing somatic items. Because somatic problems, which are related to depression, could also be caused by head and neck cancer, it is possible that their inclusion might bias the results. The results of the 2004 study, which corroborated previous findings, indicated that the somatic items did not affect the accurate identification of depression in this patient population. Our study also used the 21-item BDI (which includes the somatic items) because cutoff scores for the full survey have been investigated in previously published studies. In this study, patients who had high BDI scores on a minimum of two posttreatment surveys administered at least 6 months apart were considered to have persistent depressive symptoms. Two cutoff scores were used to differentiate normal from abnormally high levels of depressive symptoms. This study, like numerous others, uses a score of 10 or higher to screen for possible depression. On the basis of evidence from previous studies, the author of the BDI has suggested that a score of 10 or higher is an appropriate cutoff to delineate normal depressive symptoms from mild, moderate, and severe depressive symptoms in medically ill patient populations. 20,21 This study also uses a second, more conservative, cutoff score of 18. This higher cutoff, which is less likely to include many false-positive results, represents cases of probable depression. In a 2001 study that compared the BDI scores of primary medical care patients to their scores on the Patient Problem Questionnaire (PPQ), a revised version of the Primary Care Evaluation of Mental Disorders (PRIME-MD), a BDI cutoff score of 10 or higher resulted in 100% sensitivity and 70% specificity rates, whereas a cutoff score of 18 or higher resulted in 94% sensitivity and 92% specificity rates. 22 These rates were calculated on BDI scores measured at a single point in time. Because measuring depression at multiple points in time increases the likelihood of accurately identifying depression, 17 the sensitivity and specificity rates calculated in the 2001 study are not quite comparable to this study s measuring persistently high Depression in Head and Neck Cancer HEAD & NECK DOI /hed May

4 scores. However, the rates provide a baseline determination of the sensitivity and specificity of the 10þ and 18þ cutoff scores used in this study. Head and neck cancer specific performance status was measured using the Head and Neck Cancer Inventory (HNCI), a validated, self-report survey with Likert-like responses that measure severity or frequency on a 5-point scale. 23 The HNCI has 29 items that address the four separate domains of eating, speech, aesthetics, and social disruption (representing pain, socializing with friends and family, and employment). For ease of interpretation, the HNCI scores are normalized into scores ranging from 0 to 100. The data were analyzed using SPSS, version 11.5 (SPSS, Inc., Cary, NC). Descriptive statistics were used to determine the prevalence of prolonged depressive symptoms. For purposes of comparison with previously published results, an initial analysis was performed to determine the prevalence of high levels of depressive symptoms at several individual points in time. This crosssectional analysis reflects the method used in numerous prior studies that were designed to determine the prevalence of depression in the patient population with head and neck cancer. The patient sample used in this analysis included 235 patients who provided a BDI score for at least one of the four different posttreatment time periods. A longitudinal analysis was performed to determine the prevalence of high levels of depressive symptoms that persisted across time. Of the 235 patients who completed at least one BDI, 89 either died, withdrew before completing the first year, or had already completed a portion of their first year s enrollment before the BDI was administered as part of this study s battery of surveys. The longitudinal analysis addressing prolonged depressive symptoms was performed on the subset of 148 patients who provided two or more posttreatment BDI scores at least 6 months apart. This sample of 148 patients was also used in the two step-wise logistic regression analyses to identify variables associated with persistent depressive symptoms (defined as scores of 10 or higher on two or more BDIs administered at least 6 months apart). Wilcoxon rank-sum tests (for continuous data) and chi-square analyses (for categorical data) were performed first to determine the variables univariate association with persistent depressive symptoms. All variables with a p value of.1 or less were then included in the regression analyses. The first regression analysis was designed to identify which variables available before treatment could be used to predict patients at high risk of persistent depression after treatment. The pretreatment variables used in this model included patient characteristics (age, sex, pretreatment alcohol use), disease characteristics (site, stage, treatment), and pretreatment HRQOL scores (depressive symptoms, head and neck cancer specific quality of life). Stage, which represented clinical stage when pathologic stage was not available, was grouped as early (1 2) or advanced (3 4). Alcohol use at diagnosis was categorized as current, previous, or never. (No information about whether current or previous drinkers abused alcohol was available.) Treatment was grouped as either single modality or multimodality. The second regression analysis was designed to identify all factors available during the first year that are associated with persistent posttreatment depressive symptoms. This model included the pretreatment variables that were significantly associated with persistently high levels of depressive symptoms in the first multivariate analysis, as well as posttreatment head and neck cancer specific HRQOL scores and the continued use of tobacco and alcohol. Tobacco and alcohol use (categorized as current, previous, never) reflected the patients report at their last posttreatment visit. Logistic regression provides odds ratios that represent the increased likelihood of persistent depression for each statistically significant predictor. The odds ratios provided for the head and neck cancer specific and depression variables represent the increased likelihood of persistent posttreatment depression on the basis of a single-point increase in the survey score. Because a one-point difference in these scores is not clinically meaningful, the odds ratios have been exponentiated to represent the increased likelihood on the basis of the smallest, clinically meaningful difference in two survey scores. These minimally important differences for the BDI (3.69) and the four HNCI domains (eating, 5.09; speech, 5.05; aesthetics, 4.82; and social disruption, 3.40) have previously been published for the patient population with head and neck cancer. 23 RESULTS The analysis of cross-sectional prevalence rates included 235 patients who provided at least one BDI score. The analyses of prolonged depressive symptoms prevalence rates and associated fac- 456 Depression in Head and Neck Cancer HEAD & NECK DOI /hed May 2006

5 tors included the subset of 148 patients who provided two or more posttreatment BDI scores at least 6 months apart. The case-mix characteristics, type of treatment, and duration of follow-up of these two patient groups indicated that there were no substantial differences between the group of patients who filled out at least one BDI survey and the subgroup who completed two or more posttreatment BDI surveys at least 6 months apart (Table 1). Most patients were men; presented with primary, advanced-stage disease; and received multimodality therapy in the form of surgery and radiation therapy. Table 1. Pretreatment patient, disease, and treatment characteristics of patients with head and neck cancer (1) who provided at least two posttreatment BDI scores 6 or more months apart (n ¼ 148), and (2) who provided at least one BDI score (n ¼ 235). Characteristic No. of patients (%) 2 Posttreatment BDI scores 6 mo apart (n ¼ 235) 1 BDI score (n ¼ 148) Age, y <55 62 (41.9) 74 (31.5) (33.1) 79 (33.6) 66þ 34 (23.0) 78 (33.2) Unknown 3 (2.0) 4(1.7) Sex Male 99 (66.9) 165 (70.2) Female 47 (31.8) 67 (28.5) Unknown 2 (1.3) 3 (1.3) Site Oral cavity 44 (29.7) 81 (34.5) Pharynx 44 (29.7) 67 (38.5) Larynx 41 (27.8) 60 (25.5) Other/unknown 19 (12.8) 27 (11.5) Stage Early (1 2) 44 (29.7) 68 (28.9) Advanced (3 4) 92 (62.2) 150 (63.8) Unknown 12 (8.1) 17 (7.3) Presenting status Primary 121 (81.8) 182 (77.4) Recurrent 17 (11.5) 39 (16.6) Persistent 5 (3.4) 6 (2.6) Unknown 5 (3.4) 8 (3.4) Treatment Surgery only 47 (31.8) 83 (35.3) RT only 13 (8.8) 25 (10.6) Surgery þ 63 (42.6) 93 (39.6) RT (þ/ chemo) RTC 22 (14.9) 25 (10.6) Other 0 3 (1.3) Unknown 0 6 (2.6) Abbreviations: BDI, Beck Depression Inventory; RT, radiotherapy; RTC, radiation therapy and chemotherapy. Prevalence of Persistently High Depressive Symptoms. Figure 1 shows the prevalence rates of high levels of posttreatment depressive symptoms using both the 10þ and the 18þ cutoff scores. The first four columns in each of the two graphs represent rates garnered at single points in time (ie, 3, 6, 9, and 12 months). The percent of patients with posttreatment BDI scores of 10 or higher ranged from 33.6% to 44.2%, and the percent with BDI scores of 18 or higher ranged from 9.2% to 18.6% across these different time periods. The fifth column in each graph represents the rate of high levels of depressive symptoms that persisted across time (ie, for at least 6 months on two or more posttreatment BDI surveys). These longitudinal rates of persistently high levels of depressive symptoms, 25.0% for the 10þ cutoff score and 7.4% for the 18þ cutoff score, were substantially lower than the rates calculated at single points in time. (The percent of patients who never reported a high level of depressive symptoms in the longitudinal analysis was 44.6% and 78.7% for the 10þ and 18þ cutoff scores, respectively. The percent of patients who had a high level of depressive symptoms at one point in time that did not persist was 30.4% and 13.9%, respectively.) Factors Associated with Persistently High Depressive Symptoms. The findings of the univariate analyses showed that high levels of persistent depressive symptoms (defined as 10þ scores at least 6 months apart) were significantly associated (p.1) with 10 of the 18 variables (Table 2 with categorical variables and Table 3 with continuous variables). Of the 12 variables available at the time of treatment, five were significantly associated with persistent posttreatment depressive symptoms: tumors originating in the pharynx, advanced stage, multimodality treatment, a higher level of depressive symptoms at diagnosis, and a lower (worse) pretreatment HNCI social disruption score. Five of the six posttreatment variables were significantly associated with persistent posttreatment depressive symptoms: having quit drinking at some point before the posttreatment evaluation and a lower (worse) posttreatment HNCI score in all four domains (eating, speech, aesthetics, and social disruption). The first multivariate analysis included variables available at the time of treatment that were significantly associated with persistently high levels of posttreatment depressive symptoms in the univariate analyses (Table 4). Of these five variables (site, stage, treatment, pretreatment BDI Depression in Head and Neck Cancer HEAD & NECK DOI /hed May

6 FIGURE 1. Percentage of patients with high levels of posttreatment depressive symptoms based on 10þ and 18þ Beck Depression Inventory (BDI) cutoff scores. (n ¼ 235 for the cross-sectional results in the first four columns representing the percentage at or above the cutoff at 3, 6, 9, and 12 months; n ¼ 148 for the longitudinal results in the fifth persistent column representing the percentage at or above the cutoff on two or more posttreatment surveys at least 6 months apart.) BDI cutoff score Type of analysis and time period Count Cross-sectional analysis 3 mo mo mo mo Longitudinal analysis Persistently high across 6þ mo scores, and pretreatment social disruption scores), the pretreatment BDI score was the only significant factor (p ¼.0007). Higher (worse) pretreatment BDI scores were associated with persistently high posttreatment BDI scores. The odds ratio was 1.762, representing the increased likelihood of persistently high levels of posttreatment depressive symptoms for every 3.69-point increase in BDI score (which represents the smallest, clinically meaningful difference on this survey). The multivariate analysis that addressed all variables (pretreatment and posttreatment) included the five posttreatment variables that were significantly associated with persistently high depressive symptoms in the univariate analyses (ie, posttreatment alcohol use and posttreatment HNCI scores in the areas of eating, speech, aesthetics, and social disruption) (Table 5). The pretreatment BDI score was the only pretreatment variable included in this model, because it was the only variable significantly associated with persistently high posttreatment depressive symptoms in the initial multivariate analysis that addressed factors available at thetimeoftreatment. The results of the second multivariate analysis addressing pretreatment and posttreatment variables indicated that persistently high levels of posttreatment depressive symptoms were associated with higher levels of pretreatment depressive symptoms (p ¼.0859; odds ratio ¼ 1.737) as well as lower (worse) posttreatment head and neck cancer specific scores in eating (p ¼.0445; odds ratio ¼ 1.219) and social disruption (p ¼.0077; odds ratio ¼ 1.276). (These odds ratios represented the increased likelihood of persistently high levels of posttreatment depressive symptoms for every 3.69-point increase in the BDI, every 5.09-point increase in eating, and every 3.40-point increase in social disruption, which represent the smallest, clinically meaningful differences in these scores.) DISCUSSION This study investigated patients with head and neck cancer who would benefit the most from clinical intervention to manage their posttreatment depressive symptoms. Previous research has shown that depressive symptoms decrease as time from treatment increases, which strongly suggests that high levels of depressive symptoms reported at a single point in time resolve without 458 Depression in Head and Neck Cancer HEAD & NECK DOI /hed May 2006

7 Table 2. Association between persistently high levels of depressive symptoms (two or more BDI scores of 10 collected at least 6 months apart) and ordinal variables representing case-mix and treatment characteristics for patients with head and neck cancer who provided at least two posttreatment BDI scores 6 or more months apart (n ¼ 148). Ordinal variables n Persistently high, % (n ¼ 37) Not persistently high, % (n ¼ 111) Univariate p value Sex.687 Male Female Alcohol use at diagnosis.371 Current Previous Never Site.022 Oral cavity Pharynx Larynx Stage.093 Early (1 2) Advanced (3 4) Presenting status.789 Primary Recurrent/ persistent Treatment.006 Single modality Multimodality Posttreatment tobacco use.354 Current Previous Never Posttreatment alcohol use.020 Current Previous Never Abbreviation: BDI, Beck Depression Inventory. Note. Data in cells represent counts, row percentages, and p values. need for intervention. This study s method of identifying patients whose high levels of depressive symptoms persisted across time was designed to omit patients with transient problems. Although the presence of high levels of depressive symptoms 6 months apart is not necessarily indicative of a true mood disorder, depression is tied to some minimal duration of stress 17 and, when factored in, is believed to minimize false-positive results. 18 Prevalence of High Levels of Posttreatment Depressive Symptoms. The comparison of longitudinal and cross-sectional methods for assessing the prevalence of high levels of depressive symptoms demonstrated that rates obtained at single points in time were substantially larger than rates based on persistence across time. The percent of patients with scores of 18 or higher ranged from 9.2% to 18.6% for the four time periods (3, 6, 9, and 12 months after diagnosis), whereas only 7.4% had 18þ scores across 6 or more months. The difference was even larger for the 10þ cutoff score, with the longitudinal rate being 25.0% compared with the cross-sectional rates, which ranged from 33.6% to 44.2%. A longitudinal assessment of persistent depressive symptoms omits those patients whose symptoms resolve relatively quickly. It is most likely that these short-term (transient) cases have milder levels of depressive symptoms, which would account for the difference between the longitudinal and cross-sectional rates for probable depression (10þ) being larger than the difference between these rates for possible depression (18þ). Although patients identified as having possible depression (using the more liberal, 10þ cutoff score) might be questionable candidates for clinical intervention if they had been identified as having this score at only one point in time, even patients with mild depressive symptoms that do Table 3. Association between persistently high levels of depressive symptoms (two or more BDI scores of 10 collected at least 6 months apart) and continuous variables representing age at diagnosis as well as pretreatment and posttreatment health-related quality of life scores for patients with head and neck cancer who provided at least two posttreatment BDI scores 6 or more months apart (n ¼ 148). Continuous variables Persistently high (n ¼ 37) n Median score Not persistently high (n ¼ 111) n Median score Univariate p value Age Pretreatment BDI Pretreatment HNCI score Eating Speech Aesthetics Social disruption Posttreatment HNCI score Eating <.0001 Speech <.0001 Aesthetics <.0001 Social disruption <.0001 Abbreviations: BDI, Beck Depression Inventory; HNCI, Head and Neck Cancer Inventory. Note. Data in cells represent counts, median scores, and p values. Depression in Head and Neck Cancer HEAD & NECK DOI /hed May

8 Table 4. Association between persistently high levels of depressive symptoms (two or more BDI scores of 10 collected at least 6 months apart) and variables available at the beginning of treatment for patients with head and neck cancer who provided pretreatment BDI scores and at least two posttreatment BDI scores 6 or more months apart (n ¼ 77 with data for all independent variables). Independent variables included in the pretreatment model* Multivariate p value Odds ratio Site Stage Treatment Pretreatment BDI y Pretreatment social disruption Abbreviation: BDI, Beck Depression Inventory. Note. Alcohol abuse was omitted from the regression analysis because this information was available for too few patients. Limited post-hoc analyses, however, suggested that a history of problem drinking was not associated with high levels of posttreatment depressive symptoms. *Variables with p values of.1 in the univariate analysis were included as independent variables in this model. y The odds ratio represents the increased likelihood of having persistently high levels of depressive symptoms after treatment for every 3.69-point increase in the BDI score (which represents the smallest, clinically meaningful difference for this survey). not subside over 6 or more months might benefit from clinical intervention. Risk Factors for High Levels of Posttreatment Depressive Symptoms. The multivariate analysis that used only those variables available at the time of treatment indicated that the pretreatment level of depressive symptoms was the strongest independent predictor of persistently high posttreatment levels of depressive symptoms. This result is consistent with previous studies that have investigated pretreatment factors associated with posttreatment depressive symptoms that were measured at a single point in time. 6,9 The results of the second multivariate analysis, which included all pretreatment and posttreatment variables, also demonstrated that the pretreatment level of depressive symptoms was the strongest independent predictor of persistently high posttreatment levels of depressive symptoms. Posttreatment scores in eating and social disruption (which includes outcomes such as pain, socializing with friends and family, and employment) were significant, but weak, predictors of posttreatment depression. These results differ from previous studies investigating both pretreatment and posttreatment variables associated with posttreatment depressive symptoms measured at single points in time. The previous studies found posttreatment scores in head and neck cancer specific areas to be the strongest predictor of posttreatment depression. 4,15 The findings of this study probably differ from those of previous studies because the previous method of measuring posttreatment depression at single points in time included a substantial number of patients with short-term depressive symptoms. Studies measuring the prevalence of depressive symptoms at single points during the first year have found that the percentage of patients with these symptoms rises during or directly after treatment and then declines again at 12 months after diagnosis. 5,6,16 In similar fashion, head and neck cancer specific outcome scores have been shown to decrease substantially immediately after treatment, then subsequently increase to 12- month levels that approximate pretreatment levels. 23,24 The similarity of these two patterns suggests that transient depressive symptoms are likely due to problems with treatment-related outcomes and that these depressive symptoms seem to resolve as patients improve or adapt to their situation. The results of this study suggest that posttreatment depression that persists across time is largely the result of problems with this mood disorder present at the time of diagnosis, whereas concurrent, head and neck cancer specific out- Table 5. Association between persistently high levels of depressive symptoms (two or more BDI scores of 10 collected at least 6 months apart) and variables that are available across the first 12 months for patients with head and neck cancer who provided a pretreatment BDI score and at least two posttreatment BDI scores 6 or more months apart (n ¼ 67 with data for all independent variables). Independent variables included in the pretreatment and posttreatment model* Multivariate p value Odds ratio Pretreatment BDI y Posttreatment alcohol use Posttreatment eating { Posttreatment speech Posttreatment aesthetics Posttreatment social disruption { Abbreviation: BDI, Beck Depression Inventory. *This model included posttreatment variables with p values of.1 in the univariate analysis, as well as the pretreatment BDI score, because it was significantly associated with persistent depression in the previous regression analysis that included variables available at the time of treatment. y The odds ratio represents the increased likelihood of having persistently high levels of depressive symptoms after treatment for every 3.69-point increase in the BDI score (which represents the smallest, clinically meaningful difference for this survey). {The odds ratios represent the increased likelihood of having persistently high levels of depressive symptoms after treatment for every 5.09-point increase in the Head and Neck Cancer Inventory (HNCI) eating score or for every 3.4-point increase in the HNCI social disruption score (which represent the smallest, clinically meaningful differences for these domains). 460 Depression in Head and Neck Cancer HEAD & NECK DOI /hed May 2006

9 comes seem to have a much less substantial effect. These findings can be implemented in the clinical setting by using a simple and effective tool to screen for patients with high levels of pretreatment depressive symptoms. The results of this screening could be used to predict which patients are most likely to have prolonged, posttreatment depressive symptoms and benefit from intervention. The efficacy of such a screening method should be investigated in more depth, including an assessment of the most productive cutoff score for the BDI in this patient population. Acknowledgment. We acknowledge Amy Trullinger, who enrolled eligible patients and collected their data for this study. REFERENCES 1. Zabora J, Brintzenhofeszoc K, Curbow B, Hooker C, Piantadosi S. The prevalence of psychological distress by cancer site. Psychooncology 2001;10: Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA 1997;249: Baile WF, Gibertini M, Scott L, Endicott J. Depression and tumor stage in cancer of the head and neck. Psychooncology 1992;1: List MA, Mumby P, Haraf D, et al. Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer. Qual Life Res 1997;6: D Antonio LL, Long SA, Zimmerman GJ, Peterman AH, Petti GH, Chonkich GD. Relationship between quality of life and depression in patients with head and neck cancer. Laryngoscope 1998;108: Hammerlid E, Ahlner-Elmqvist M, Bjordal K, et al. A prospective multicentre study in Sweden and Norway of mental distress and psychiatric morbidity in head and neck cancer patients. Br J Cancer 1999;80: de Graef A, de Leeuw JRJ, Ros WJG, Hordijk GJ, Blijham GH, Winnubst JAM. Pretreatment factors predicting quality of life after treatment for head and neck cancer. Head Neck 2000;22: de Graeff A, de Leeuw RJ, Ros WJG, Hordijk GJ, Blijham GH, Winnubst JAM. Sociodemographic factors and quality of life as prognostic indicators in head and neck cancer. Eur J Cancer 2001;37: de Leeuw JRJ, de Graeff A, Ros WJG, Blijham GH, Hordijk GJ, Winnubst JAM. Prediction of depression 6 months to 3 years after treatment of head and neck cancer. Head Neck 2001;23: Duffy SA, Terrell JE, Valenstein M, Ronis DL, Copeland LA, Connors M. Effect of smoking, alcohol, and depression on the quality of life of head and neck cancer patients. Gen Hosp Psychiatry 2002;24: Katz MR, Kopek N, Waldron J, Devins GM, Tomlinson G. Screening for depression in head and neck cancer. Psychooncology 2004;13: Bjordal K, Kaasa S. Psychological distress in head and neck cancer patients 7 11 years after curative treatment. Br J Cancer 1995;71: Kugaya A, Akechi T, Okamura H, Mikami I, Uchitomi Y. Correlates of depressed mood in ambulatory head and neck cancer patients. Psychooncology 1999;8: Cornelius JR, Bukstein O, Salloum I, Clark D. Alcohol and psychiatric comorbidity. Recent Dev Alcohol 2003;16: de Leeuw RJ, de Graeff A, Ros WJG, Blijham GH, Hordijk GJ, Winnubst JAM. Prediction of depressive symptomatology after treatment of head and neck cancer: the influence of pre-treatment physical and depressive symptoms, coping, and social support. Head Neck 2000;22: de Boer MF, Pruyn JFA, van den Borne B, Knegt PP, Ryckman RM, Verwoerd CDA. Rehabilitation outcomes of long-term survivors treated for head and neck cancer. Head Neck 1995;17: Kendall PC, Hollon SD, Beck AT, Mammen CL, Ingram RE. Issues and recommendations regarding use of the Beck Depression Inventory. Cogn Ther Res 1987;11: Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289: Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4: Schwab JJ, Bialow M, Brown JM, Holzer CE. Diagnosing depression in medical inpatients. Ann Intern Med 1967;67: Beck AT, Beamesderfer A. Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiat 1974; 7: Arnau RC, Meagher MW, Norris MP, Bramson R. Psychometric evaluation of the Beck Depression Inventory-II with primary care medical patients. Health Psychology 2001; 20: Funk GF, Karnell LH, Christensen AJ, Moran PJ, Ricks J. Comprehensive head and neck oncology health status assessment. Head Neck 2003;25: de Graef A, de Leeuw JRJ, Ros WJG, Hordijk GJ, Blijham GH, Winnubst JAM. A prospective study on the quality of life of patients with cancer of the oral cavity or oropharynx treated with surgery with or without radiotherapy. Oral Oncol 1999;35: Depression in Head and Neck Cancer HEAD & NECK DOI /hed May