Depression and Anxiety in Patients With Cancer: A Cross-Sectional Study

1In cancer patients, psychological problems such as depression and anxiety persist and can cause an additional burden during their treatment, making it more challenging in terms of its management and control, compliance during the treatment course, duration of hospital stay, and, ultimately, survival rate. Previous studies have reported that the prevalence of depressive disorders among cancer patients is two to three times higher than those of the general population. Previous studies that evaluated psychological distress among cancer patients have reported various heterogeneous prevalence rates that differed according to clinical settings (outpatient clinics, hospital settings, and palliative care), stage of the disease (newly diagnosed, recurrence, survivorship, or advanced stages), and phase of treatment, which ranged between 5.0 and 49.0%. A previous meta-analysis that explored the prevalence of depression among cancer patients and included 211 studies (representing more than 82,000) reported a different prevalence rate of depression—one that differed by the type of instrument, type of cancer, and treatment phase. In addition, the prevalence rate of depressive disorders among cancer patients differed by cancer site and ranged from 5.6% for patients with genitourinary cancer to 13.1% for patients with lung cancer. Furthermore, depression is more common among patients with severe illness and advanced stages of malignancy. A previous critical review that included 11 previous systematic reviews and meta-analyses, which aimed to identify risk factors of depression among cancer patients, has reported a wide range of factors that play a key role in developing depression besides the biological factors (the type of cancer, stage of the disease, and treatment-related factors). This includes individual factors (family history, personal psychiatric history, and personality traits) and interpersonal and social factors (a history of stressful life events, loneliness, social isolation, low-socioeconomic status, and lack of social support). Assessment of psychological distress among cancer patients is important in order to recognize patients who need help and further assessment and, therefore, subsequent healthcare intervention. This increasingly highlights the fact that depression is a substantial problem in cancer patients.

2In 2018, a total of 10,898 new cancer cases were diagnosed in Jordan within a population of 9,903,798. An age-standardized incident rate was 157.8 per 100,000, while the age-standardized mortality rate was 89.7 per 100,000. The top five most prevalent cancers were breast cancer, lung cancer, colorectal cancer, bladder cancer, and leukemia. Even though depression is a significant complication of cancer and its occurrence is higher than in the general population, it is often neglected. Studies on the prevalence of depression and anxiety among cancer patients in the Middle East are limited, with many limitations such as small sample size and being restricted to a specific type of cancer in specific clinical settings. The primary aim of this study is to describe the prevalence and risk factors of depressive and anxious symptomatology in cancer patients in the inpatient and outpatient settings. Additionally, we aimed to explore the pattern of use of antidepressants among the study participants. This will enable us to identify cancer patients who are at higher risk of depression and anxiety. Mental and medical support can be directed to cancer patients who are at higher risk in order to control their psychological problems and improve their clinical outcome. Early identification is critical in the management of depressive symptoms and plays an important role in improving their adherence to the therapy and the overall control of the disease.

3This was a cross-sectional study conducted at the King Hussein Cancer Center (KHCC) in Amman, Jordan, between October 2019 and February 2020. According to the last available statistics in 2015, KHCC provides medical care to around 60.0% of all cancer patients in Jordan. KHCC is the main hospital and the single specialized tertiary hospital in Jordan and provides comprehensive clinical management and cancer care to adults and pediatric patients from Jordan and the surrounding region.

4Data were collected from the inpatient and outpatient settings using a convenience sampling technique. Cancer patients who have any type of cancer from any stage and who are willing to participate in the study formed the study population. The inclusion criteria were (a) patients aged 18 years and above with a confirmed cancer diagnosis and (b) patients who had no apparent cognitive deficit. Patients were excluded if they were (a) below 18 years of age and (b) unable to participate in this study due to physical or emotional distress. This is due to the difficulties in detecting depression in cancer patients with emotional distress because of patients’ reluctance to discuss their emotional well-being. Eligible patients were identified and assessed by a clinical pharmacist (NM). Recruitment of patients was conducted by two pharmacists (AH and NM). For patients who agreed to participate, the study’s aim and objectives were explained thoroughly. Information sheets were provided to the patients for further clarification about the study. In addition, patients were informed that their agreement to participate in the study is considered as written consent. Patients’ clinical data were obtained from their medical charts in collaboration with a clinical pharmacist at the cancer center.

5The target sample size was estimated based on the WHO recommendations for the minimal sample size needed for a prevalence study. Using a confidence interval of 95%, a standard deviation of the prevalence rate of 0.5, a margin of error of 5%, we determined that the required sample size was 385 patients.

6Previously validated assessment scales, the Patient Health Questionnaire (PHQ)-9, Generalized Anxiety Disorder 7-item (GAD-7) scale, and Hospital Anxiety and Depression Scale (HADS) were used to assess depressive and anxious symptomatology among the study participants. These screening instruments were frequently used and validated as brief screening tools among cancer patients for depressive and anxious symptomatology. These assessment scales provide a symptomatological assessment based on predefined cut-off points.

7Different assessment scales were used to fit the inpatient and outpatient settings, as recommended by previous literature. The HADS and GAD-7 instruments were previously validated to be used for hospitalized patients (secondary care settings) in multiple previous studies, including studies on patients with cancer. In contrast, the PHQ-9 and GAD-7 instruments were recommended for patients in primary care settings. The PHQ-9 scale is a nine-question instrument given to patients in a primary-care setting to screen for the presence and severity of depressive symptomatology. This instrument was used to assess depressive symptomatology among cancer patients in the outpatient setting, and the GAD-7 instrument was used to screen for anxiety among them. In the inpatient setting, the HADS instrument was used, which is a 14-question instrument given to patients in a secondary-care setting to screen for the presence and severity of depressive and anxious symptomatology.

8The use of a pre-existing scale has the advantage of using a validated and tested instrument, which increases the reliability of its measure. The PHQ-9 and the GAD-7 instruments ask the patients about the degree of applicability of each item (question), using a 4-point Likert scale. Patients’ responses ranged from 0 to 3, where 0 means “Not at all” and 3 means “Nearly every day.” The HADS instrument is a 14-question questionnaire that asks the patients about the degree of applicability of each item (question), using a 4-point Likert scale. Patients’ response ranges from 0 to 3, where 0 means “Often” and 3 means “Very seldom” or from “Not at all” to “Most of the time.”

9Prevalence rates of depressive and anxious symptomatology were determined using a cut-off point as recommended by the authors of the PHQ-9, GAD-7, and HADS scale. At the inpatient setting using the HADS instrument, depressive and anxious symptomatology were defined as a total score of (10 or more) at “depression subscale” or “anxiety subscale,” respectively. At the outpatient setting, depressive symptomatology was defined as a total score of 15 and above in the PHQ-9 instrument, indicating a case with moderately severe or severe depression. Anxious symptomatology was defined using the GAD-7 instrument with a total score of 15 and above, indicating a case with severe anxious symptomatology. The higher the score, the more severe the case identified by any scale.

10The prevalence rate of depressive symptomatology was estimated by dividing the number of patients who exceeded the borderline score by the total number of patients. The same procedure was followed to calculate the prevalence rate of anxious symptomatology in the inpatient and the outpatient settings.

11The HADS instrument was used in the inpatient setting, which includes two subscales (anxiety and depression) with seven items for each. Items are scored from 0 to 3, generating a total score ranging from 0 to 21 on each subscale. A total score of 0–7 indicates a normal case, 8–10 a borderline case, and 11–21 an abnormal case of depressive or anxious symptomatology according to the subscale score. In addition, anxious symptomatology was assessed using the GAD-7 scale as a second measure and results were compared with HADS.

12The PHQ-9 instrument was used in the outpatient setting, which includes nine items. Items are scored from 0 to 3, generating a total score ranging from 0 to 27. A total score of 0–4 indicates minimal depression, 5–9 mild depression, 10–14 moderate depression, 15–19 moderately severe depression, and 20–27 severe depression. The GAD-7 instrument includes seven items. Items are scored from 0 to 3, generating a total score ranging from 0 to 21. A total score of 5–9 indicates mild anxiety, 10–14 moderate anxiety, and 15–21 severe anxiety.

13Descriptive statistics were used to describe patients’ demographic characteristics, medication use, and comorbidities. Continuous data were reported as mean ± SD. Categorical data were reported as percentages (frequencies). Logistic regression was used to estimate odds ratios (ORs), with 95% confidence intervals (CIs) for anxious or depressive symptomatology. Logistic regression models were carried out using anxious or depressive symptomatology scores above the cut-off points as highlighted in the section “Materials and Methods.” The cut-off point for the PHQ-9 and GAD-7 scale that was used to identify severe depressive symptomatology and severe anxious symptomatology in the outpatient setting was 15 and above. The cut-off for the HADS scales that was used to identify depressive symptomatology and anxious symptomatology in the inpatient setting was 10 and above (whether for the depression or anxiety subscale). A two-sided p < 0.05 was considered statistically significant. The statistical analyses were carried out using SPSS for Windows (version 25).

14Out of 1,041 patients who were approached during the study period, a total of 1,011 patients (response rate of 97.1%) participated in the study: inpatient setting = 399, outpatient setting = 612. Table 1 details the baseline characteristics of the patients in the inpatient and outpatient settings. The mean age of the patients was 54.9 years (±15.2). The majority of patients (n = 560, 55.4%) were males, married (n = 833, 82.4%), and unemployed (n = 471, 46.6%), with an income of 500 JD or below (n = 737, 72.9%). Around 18.4% (n = 186) of the patients reported that their cancer was metastatic. More than half (n = 566, 56.0%) of the patients reported being treated with chemotherapy.

15The most common cancer type in the study was blood cancer (n = 196, 19.3%), followed by colorectal cancer (n = 178, 17.6%) and lung cancer (n = 120, 11.9%). Please refer to Supplementary Table 1, which shows the distribution of cancer types among study participants.

16Around 42.7% (n = 432) and 24.8% (n = 251) of the patients reported that they feel anxious and depressed, respectively, and only 15.5% (n = 39) of them were using antidepressants. The two most commonly used antidepressant medications were sertraline (29.0%, n = 9) and citalopram (16.1%, n = 5).

17The mean age of the patients when they started using antidepressants was 52.2 years (±17.4). Around 51.6% (n = 16) of these patients were using antidepressants last year, and 67.7% (n = 21) are using it currently. The majority of the patients (80.6%, n = 25) were using antidepressant medications under medical supervision. The main indication for the use of antidepressants was to alleviate depression for 83.9% (n = 26), and 35.5% (n = 11) were using them to alleviate anxiety. Around 92.3% (n = 36) of the patients reported that they had received instructions on how to use antidepressants. The main source of these instructions was a physician (94.4%, n = 34). The majority of the patients (75.0%, n = 27) believe that these instructions are important (Table 1).

18The main reasons patients consider the healthcare professionals’ instructions important include the notion that they increase the safety (27.3%, n = 6) and effectiveness (27.3%, n = 6) of the medication; they decrease side effects and drug interactions (27.3%, n = 6) and increase confidence in therapy (18.2%, n = 4). Nine patients reported that they have questions about antidepressants, and they were mainly considering treatment side effects, mechanisms of action, and treatment time (Supplementary Table 2).

19Supplementary Table 3 highlights characteristics of antidepressant use and patient knowledge. More than half of the patients (56.8%, n = 21) reported that they have increased the dose of antidepressant medication without consulting the doctor. Around 40.5% (n = 15) of the patients reported that they were experiencing side effects from the use of antidepressants. The main three side effects were nausea, dizziness, and insomnia, suffered by 73.3%, 60.0%, and 40.0% of patients, respectively. About 29.7% (n = 11) and 21.6% (n = 8) of the patients reported that they think that antidepressant use can cause addiction and tolerance, respectively. More than half of the patients (59.5%, n = 22) reported that antidepressant therapy should gradually be withdrawn at the end of the treatment. When the patients were asked about whether they had stopped using antidepressant without consulting the doctor, 32.4% (n = 12) reported they had. The two most common reasons for this practice were improved depressive symptoms (50.0%, n = 6) and low tolerance of side effects of the medication (41.7%, n = 5).

20The prevalence of depressive symptomatology among all patients was 23.4% (n = 237; 89 from the outpatient setting and 148 from the inpatient setting). Depressive symptomatology was more prevalent in the inpatient setting (37.1%; n = 148) compared to the outpatient setting (14.5%; n = 89). The prevalence of anxious symptomatology among all patients was 19.1% (n = 193) using the HADS for the inpatients or 19.9% (n = 201), using the GAD-7 for the inpatients. Similarly, anxious symptomatology was more prevalent in the inpatient setting, at 35.6% (n = 142), using the HADS, or 37.6% (n = 150) (using the GAD-7). Table 2 below details the prevalence of depressive and anxious symptomatology among the patients stratified by severity.

21Table 3 below details the prevalence of depressive and anxious symptomatology stratified by severity and type of cancer in the inpatient and the outpatient setting. In the inpatient setting, depressive symptomatology was more common across patients with bladder cancer, and severe anxious symptomatology was more prevalent among patients with lung cancer. In the outpatient setting, depressive symptomatology was more common among patients with breast cancer, and the highest prevalence of anxious symptomatology was among patients with prostate cancer.

22In the inpatient setting, logistic regression analysis identified the following groups as being at a higher risk of depressive symptomatology: a) patients with metastatic cancer, OR: 2.62 (95% CI 1.61–4.28) and b) patients at an advanced stage of the disease, stage 3, OR: 5.26 (95% CI 1.05–26.41) and stage 4, OR: 2.73 (95% CI 1.61–4.62). In the outpatient setting, patients with metastatic cancer were the only group that showed a statistically significant increased risk of depressive symptomatology, OR: 3.36 (95% CI 1.33–8.50), compared with others.

23Regarding anxious symptomatology, in the inpatient setting the following groups were identified to be at a higher risk using the HADS: a) patients with metastatic cancer, OR: 2.10 (1.29–3.42) and b) patients at stage four of the disease, OR: 2.39 (95% CI 1.42–4.04). On the other hand, patients who are treated with a combination of chemotherapy and surgery showed a lower risk of anxious symptomatology, OR: 0.54 (95% CI 0.33–0.86). On the basis of the GAD-7 scale, the only patient group that showed a higher risk of anxious symptomatology was the group with metastatic cancer, OR: 2.23 (95% CI 1.32–3.74). In the outpatient setting, unemployed patients—OR: 1.89 (95% CI 1.03–3.35)—and patients with metastatic cancer—OR: 2.47 (95% CI 1.15–5.33)—were at higher risk of anxious symptomatology (Table 4).

24This study aimed to identify the prevalence of depressive and anxious symptomatology among cancer patients and to identify key risk factors using validated assessment tools. Additionally, we explored the pattern of use of antidepressants among the study participants. Several dimensions were investigated in this study, including patients’ characteristics, the prevalence of anxious and depressive symptomatology according to the type of cancer and treatment settings (inpatient versus outpatient). Our findings showed that the prevalence of depressive and anxious symptomatology among cancer patients was 23.4% and 19.1–19.9%, respectively. Increased likelihood of depressive and anxious symptomatology was detected among patients in the inpatient setting (37.1% and 35.6–37.6%, respectively). Screening of frequently prescribed anxiolytics and antidepressants was investigated, revealing that for the most part, SSRIs were prescribed, but as low as 15.5% of depressed and anxious patients received the required treatment.

25Our research employed two validated tools (GAD-7 and HADS) to assess the prevalence of anxiety among cancer patients in the inpatient setting, and both of them were reliable and showed a significant correlation (correlation coefficient: 0.812) in terms of the prevalence of anxiety (37.6% versus 35.6% in the inpatient setting). The increased cancer-specific depressive symptomatology was noted across settings (inpatient and outpatient) and was significantly higher in the inpatient settings.

26Several factors may impact the development of depression and anxiety among cancer patients, including the cancer type, stage, grade, and treatment option. Interestingly, our results are aligned with the findings of several studies, where specific tumor types can lead to depression and anxiety, particularly head and neck, lung, breast, and prostate cancer, which, in our research, showed that depression and anxiety are more prevalent in the inpatient setting in patients with head and neck cancer, lung cancer, and bladder cancer, while in the outpatient setting, they were more prevalent among patients diagnosed with prostate and breast cancer.

27In addition to the type of cancer, the treatment option impacted the prevalence of anxiety and depression among cancer patients. Cancer treatments that entail chemotherapy may induce depression through specific biological mechanisms. Furthermore, the literature reported that antiemetic medications, steroids, and androgen suppression therapy (for prostate cancer) were reported to induce depression. The findings of our study revealed that most cancer patients receive chemotherapy alone (56.0%) or chemotherapy and surgery (34.8%), thus increasing their risk of depression and/or anxiety. The use of chemotherapy-induced nausea and vomiting (CINV) medications, as well as steroids, are a mainstay for the prevention and treatment of CINV and, consequently, contribute to the high prevalence of anxiety and depression among cancer patients.

28This study also explored the pattern of use of antidepressants among cancer patients stratified by type, where the rate of using antidepressants among patients diagnosed with depression was as low as 15.5%. Low use of antidepressant therapy is an alarming sign, especially for cancer patients who are receiving specialized cancer services. Antidepressants should be introduced as soon as the patient is diagnosed with depression. Use of antidepressants should be individualized according to the patient’s health profile to address his or her symptoms. The choice of antidepressants should be based on the patient’s concurrent medications, history, and symptoms. Pharmacological therapy is recommended for patients with severe depression, while patients with mild to moderately severe depression are recommended to receive psychotherapy. Several behavioral approaches can be implemented to improve the psychological status of cancer patients, such as cognitive behavioral therapy, mindfulness-based approaches, and self-management strategies. Management of depression and treatment initiation should be under medical supervision, due to the nature of antidepressants and the high probability of drug-drug interaction, adverse effects, and the need for dose adjustment.

29The majority of patients were prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants (sertraline, citalopram, fluoxetine, fluvoxamine, and paroxetine), while tetracyclic antidepressants (mirtazapine) and tricyclic antidepressants (amitriptyline) were prescribed to a lesser extent. The selection of an anxiolytic or antidepressant medication needs to be made under clear guidelines that consider interactions with chemotherapeutic and other concurrently administered medication, as well as side effects, to enable identification of specific contraindications. Sertraline and citalopram are usually recommended for depression and anxiety treatment, as they have the least tendency for interactions and are usually well tolerated. Although the use of medications for depression and anxiety among cancer patients in this study was low, the selection of pharmacological agents is in line with the above recommendations. However, a patient-centered approach and a customized treatment plan need to be considered, as studies reported that the SSRIs need to be avoided in elderly patients due to the risk of hyponatremia. Fluoxetine and paroxetine are contraindicated in patients being treated with tamoxifen. Furthermore, mirtazapine should be avoided where white blood cells are compromised and SSRIs are to be avoided where platelets are compromised. Finally, since almost 70.0% of the patients reported that they experienced nausea, SSRIs need to be avoided as this will augment chemotherapy-induced nausea and vomiting.

30Our findings suggest that severe depressive and anxious symptomatology are substantially more common in patients with cancer in the inpatient than in the outpatient setting. This significant difference could be attributed to the severity of the disease, where hospitalized treatment of cancer patients is mainly employed for the management of acute phases, initial onsets, severe cases, or late stages. A previous study involving more than 5,000 patients has reported that more symptoms of anxiety are associated with cancer within the inpatient setting and in patients in the advanced stages, whereas patients at early stages demonstrated lower anxiety symptoms. Furthermore, disease stage was associated with depression, particularly in men.

31Further analysis using logistic regression was conducted to identify patients at risk of developing depressive and anxious symptomatology. Similar to reported data, the prevalence of anxiety and depression among women is higher than in men. As discussed earlier, the advancement of the stage of the disease has an impact on depression and anxiety. Patient vulnerability exacerbates the ability to become depressed and anxious, which is reported to be caused by some socioeconomic factors and disease stages. Such results align with our findings about patients with metastasis, advanced disease stages, and lower-income were more vulnerable to developing anxiety and/or depression. Such findings support the need to consider mental disorders as part of the treatment protocol for cancer patients and calls for enhanced clinical monitoring and treatment of depression and anxiety symptoms among cancer patients.

32To the best of our knowledge, this is the first and largest study in the Middle East region to investigate the prevalence of depressive and anxious symptomatology and use of antidepressants among cancer patients without restriction on the type of cancer or clinical settings. Previous studies have focused on a specific type of cancer (breast cancer and colorectal cancer) and had a small sample size (not more than 100 patients).

33We have explored the prevalence of depressive and anxious symptomatology among cancer patients without any restriction on the age, gender, duration of the disease, or treatment phase. Our broad inclusion criteria have enabled us to explore the difference in severity of depressive and anxious symptomatology among different demographic groups and across different stages of the treatment and the course of illness. This study has many strengths that increase its value and reliability: (a) using validated assessment tools for depressive and anxious symptomatology, (b) anxious symptomatology was assessed using two assessment tools (HADS and GAD-7), and both of them showed consistent findings, (c) employing a large sample size, (d) not restricting the inclusion criteria for the specific type of cancer or specific settings (inpatients or outpatients), which increased the generalizability of our findings, and (e) our exclusion criteria minimized the risk of deriving imprecise information (related to the patients’ psychological status) from any suspected physical or emotional distress. On the other hand, this study has limitations: (a) the study design itself, a cross-sectional study design, limited our ability to identify causality between study variables, as it is only capable of showing an association between variables, and (b) the sample size of a few cancer subgroups was small due to a small population in this category nationwide. This might affect our ability to determine the prevalence of depressive and anxious symptomatology among patients with specific types of cancer, especially types for which we have a very low number of patients, such as head and neck cancer; (c) the use of convenience sampling techniques might affect the generalizability of our findings as a prevalent study and may introduce sampling bias (which might not precisely represent the targeted population); (d) the use of different assessment tools to describe the prevalence of depressive symptomatology between the inpatient and the outpatient settings might not provide a fair comparison; (e) there is a lack of non-responder data; and (f) the antidepressant medication information is based on small subsamples making conclusions difficult to sustain. Therefore, our findings should be interpreted carefully.

34Our study demonstrated a higher prevalence of both depressive and anxious symptomatology within the inpatient setting and advanced stages of the disease. There is a need for cancer management clinical guidelines to consider early assessment and management of depression and anxiety and to continue to monitor it throughout treatment.

35The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

36Approval for this study was obtained from the Institutional Review Board Committee at King Hussein Cancer Centre in Jordan (No. 19 KHCC 94). For patients who agreed to participate, the study’s aim and objectives were explained thoroughly. Information sheets were provided to the patients for further clarification about the study. In addition, patients were informed that their agreement to participate in the study is considered as a written consent.

37AN contributed to the study design and did the data analysis. AN, AH, NM, and HK conducted the study and collected the data. AN, ED, NM, and HA wrote the first draft of the article. AN, HA, ED, HA, and NM were involved in interpretation of the data. All authors reviewed the manuscript for important intellectual content, provided final approval of the version to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

38The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.