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Prevalence and risk factors of insomnia in solid tumor patients in a tertiary care hospital

  • Amrita Asok
    Affiliations
    Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India
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  • Anagha C. C
    Affiliations
    Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India
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  • Radhika T. K
    Affiliations
    Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India
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  • Sreelakshmi Sreekumar
    Affiliations
    Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India
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  • Merin Babu
    Affiliations
    Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India
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  • Uma Devi Padma
    Correspondence
    Corresponding author.
    Affiliations
    Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India
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  • Keechilat Pavithran
    Correspondence
    Corresponding author. Department of Medical Oncology and Hematology, Amrita Institute of Medical Science and Research Centre, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India.
    Affiliations
    Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, 682 041, Kerala, India
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Open AccessPublished:March 19, 2022DOI:https://doi.org/10.1016/j.cegh.2022.101014

      Abstract

      Background

      Though cancer-related insomnia is a grave issue, it is often overlooked by caregivers and patients alike. This study examined insomnia's prevalence in solid tumor patients and the risk factors associated with it.

      Methods

      The prevalence of insomnia and overall sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI). The Hospital Anxiety and Depression Scale (HADS) aided in measuring anxiety and depression, while the Wong-Baker FACES® Pain Rating Scale was employed to measure pain. Analysis was carried out using SPSS 21.0 version software.

      Result

      The prevalence of insomnia over two months in a group of solid tumor patients comprising 56 (34.1%) males and 108 (65.9%) females with a mean age of 57.72 ± 12.78 years was found to be 65.9%, and the group's mean PSQI score was 9.12 ± 5.38. The mean anxiety, depression, and pain scores were 7.60 ± 4.09, 7.50 ± 4.07, and 2.51 ± 2.78, respectively. We found a significant influence of anxiety, depression, and pain on insomnia (P < 0.001 for all three parameters).

      Conclusion

      More than 50% of the patients were poor sleepers, and there were significant positive associations of anxiety, depression, and pain (P < 0.001) with insomnia.

      Keywords

      1. Introduction

      Sleep is fundamental for the normal functioning, repair, and maintenance of the body, and sleep disturbances can adversely affect a person's physical and mental well-being. Quality of life (QOL), which is a cluster of physical, psychological, and social well-being, is one of the markers that treating physicians focus on for their patients.
      • Purkayastha D.
      • Venkateswaran C.
      • Nayar K.
      • Unnikrishnan U.G.
      Prevalence of depression in breast cancer patients and its association with their quality of life: a Cross-sectional observational study.
      Many studies have shown bi-directional correlations of pain, anxiety and depression with insomnia, and vice versa. This may explain why patients with solid tumors experience insomnia frequently, which is often not given due importance.
      • Jansson-Fröjmark M.
      • Lindblom K.
      A bidirectional relationship between anxiety and depression, and insomnia? A prospective study in the general population.
      ,
      • Jansson-Fröjmark M.
      • Boersma K.
      Bidirectionality between pain and insomnia symptoms: a prospective study.
      To date, there is very little data providing a clear-cut prevalence of insomnia in cancer patients. A lot of patients with cancer are relatively old and have other co-existing diseases. This, along with the burden of cancer therapy, takes a toll on these patients and decreases their functioning ability. Patients with cancer report a variety of symptoms, with pain, fatigue, insomnia, and mood disturbances topping the list throughout the disease and treatment periods. Also, a point to be noted is that these symptoms mostly occur alongside each other rather than in isolation. A combination of all these problems can negatively affect the patient and his/her outcomes. Though numerous studies have tried to shed light on the association between insomnia and other factors like age, gender, type of cancer, and treatment approach, the results have been conflicting.
      • Asok A.
      • Sreekumar S.
      • Radhika T.K.
      • Anagha C.C.
      • Uma Devi P.
      • Pavithran K.
      Effectiveness of zolpidem and sleep hygiene counseling in the treatment of insomnia in solid tumor patients.
      The purpose of our study was to determine the prevalence and risk factors associated with insomnia in solid tumor patients. This would help draw attention to this grave problem and the need for better treatment alternatives.
      • Beck S.L.
      • Schwartz A.L.
      • Towsley G.
      • Dudley W.
      • Barsevick A.
      Psychometric evaluation of the Pittsburgh sleep quality Index in cancer patients.

      2. Patients and methods

      This was a single-centred questionnaire-based prospective observational study conducted in the Medical Oncology Department of a tertiary care hospital in Kochi. The protocol for conducting the study was approved by the ethical committee of the institution (IEC-AIMS-2017- PHRM 150). In total, 526 patients were screened to assess the prevalence of insomnia. After preliminary exclusions, 164 patients who satisfied the inclusion criteria were selected to participate. Inclusion criteria included being above the age of 18 years and the ability to read, write, and speak either English or Malayalam. Patients who were not willing to give consent or who had hematological malignancies were excluded from the study.
      All included patients were asked to complete the Pittsburgh Sleep Quality Index (PSQI) to assess their overall sleep quality, the Hospital Anxiety and Depression Scale (HADS) to measure anxiety and depression, and the Wong-Baker FACES® Pain Rating Scale to assess pain in the cancer population. The demographic details, as well as other relevant data required for the study, were obtained by direct patient interviews and using the Amrita Health Information System (AHIS). The collected data were then transcribed into a specifically designed data collection form. The form included demographic details, primary diagnosis, cancer stage, current treatment (chemotherapy, radiotherapy, or hormone therapy), any recent surgeries (within the past two months), duration from the diagnosis of cancer, other co-morbidities, patient problems (for example, pain, gastric irritation, itching, cough, breathlessness, nocturia) and other personal details including education level, and marital status. In our study, we tried to assess whether cancer, its therapy, and other personal factors had any impact on the development and progression of insomnia in these patients.
      The PSQI is a sleep questionnaire designed to judge sleep quality over a month. It consists of 19 self-report questions that sum up to yield a score ranging from 0 to 21, with a score of 21 indicating the worst sleep quality. A cut-off score of 5 differentiates normal and poor sleepers. The questionnaire also evaluates subjective quality, latency, efficiency, duration, and disturbances in sleep along with sleep medication consumption and daytime dysfunction. The PSQI global score was used to measure the prevalence of insomnia in this subset of the population. Patients with a global PSQI score of <5 were categorized as normal sleepers.
      • Davis M.P.
      • Khoshknabi D.
      • Walsh D.
      • Lagman R.
      • Platt A.
      Insomnia in patients with advanced cancer.
      The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression. It contains two sets of questions that measure anxiety and depression (seven components for each set). Each question is indexed on a 4-point scale. Both the anxiety (HADS-A) and depression (HADS-D) indexes have a range of total scores from 0 to 21, with 21 indicating the most severe anxiety or depression. A score of ≤7 is classified as ‘normal’, scores ranging from 8 to 10 are classified as ‘borderline’, and scores of ≥11 are classified as ‘abnormal’.
      • Jadhav S.A.
      • Sukumar S.
      • Kumar G.
      • Bhat S.H.
      Prospective analysis of psychological distress in men being investigated for prostate cancer.
      Pain ratings were attained using the Wong-Baker FACES pain rating scale after obtaining permission from the owner. The scale depicts a series of emoticons ranging from a happy face at 0 “no pain” to a crying face at 10 “hurts the worst”. The patients were instructed to choose the face that best described how much pain they were in. Analysis was carried out using SPSS 21.0 version software. The data are presented as frequency and percentage.

      3. Results

      The mean age of our population (n = 164) was 57.72 ± 12.78 years, with most patients in the age group of 40–60 years. Of the patients, 56 (34.1%) were male [Table 1].
      Table 1General characteristics of patients.
      CharacteristicsNumber (n = 164)Percentage (%)
      Age groups
      <40 yrs159.1
      40–60 yrs8149.4
      >60 yrs6841.5
      Gender
      Male5634.1
      Female10865.9
      Menopausal status
      Pre-menopausal4238.9
      Post-menopausal6661.1
      Marital status
      Married14286.6
      Single/Divorced/Widow2213.4
      Educational status
      Educated14286.6
      Illiterate2213.4
      Cancer type
      Breast6237.8
      Gastrointestinal3118.9
      Lung1911.6
      Gynecological1710.4
      Lymphoma127.3
      Head and Neck116.7
      Prostate31.8
      Others95.5
      Stage
      I42.4
      II3823.2
      III5432.9
      IV6841.5
      Metastasis
      Localized9658.5
      Metastasized6841.5
      Surgery
      Yes2414.6
      No14085.4
      Therapy
      Chemotherapy8753
      Radiation therapy2817.1
      Hormonal therapy2414.6
      No therapy2515.2
      Time from diagnosis
      <1 year8954.3
      1–5 years6539.6
      6–10 years95.5
      >10 years10.6
      Co-morbidities
      Hypertension6338.4
      Diabetes mellitus5231.7
      Dyslipidemia1911.6
      Respiratory diseases169.8
      GI and hepatic diseases159.1
      Heart diseases137.9
      Thyroid diseases84.9
      Others2917.7
      Other factors
      Alcoholic63.7
      Smoking95.5
      Caffeinated drinks3923.8
      Cough4426.8
      Dyspnoea4527.4
      Acidity3118.9

      4. Prevalence of insomnia

      The mean PSQI score of the study population was 9.12 ± 5.38. Out of 164 patients, 108 (65.9%) were poor sleepers with PSQI scores of >5.

      4.1 Risk factors of insomnia

      • a)
        Age and gender
      The majority of patients in the insomnia group (51.9%) were in the age group of 40–60 years. A greater proportion of males (36.1%) belonged to insomniacs when compared to normal sleepers. Most of the female participants (69.6%) did not complain of insomnia. However, when compared to males, insomnia was found to be more prevalent in females. Post menopausal females (65.2%) were also higher in insomnia group. Age and gender showed no significant correlation with insomnia [Table 2].
      • b)
        Co-morbidities
      Table 2Factors and their relationship with Insomnia.
      FactorsInsomnia (n = 108) (%)No Insomnia (n = 56) (%)P value
      Age
      <40 yrs7 (6.5)8 (14.3)0.241
      40–60 yrs56 (51.9)25 (44.6)
      >60 yrs45 (41.7)23 (41.1)
      Male39 (36.1)17 (30.4)0.461
      Female69 (63.9)39 (69.6)
      Post-Menopausal45 (65.2)21 (53.8)0.266
      Pre-Menopausal24 (34.8)18 (46.2)
      Breast36 (33.3)26 (46.4)0.309
      Gastrointestinal21 (19.4)10 (17.9)
      Lung16 (14.8)3 (5.4)
      Gynaecological11 (10.2)6 (10.7)
      Lymphoma6 (5.6)6 (10.7)
      Head and Neck8 (7.4)3 (5.4)
      Prostate2 (1.9)1 (1.8)
      Stage I3 (2.8)1 (1.8)0.863
      Stage II23 (21.3)15 (26.8)
      Stage III36 (33.3)18 (32.1)
      Stage IV46 (42.6)22 (39.3)
      Time of diagnosis

      <1year
      61 (56.5)28 (50)0.719
      Time of diagnosis

      1–5 years
      40 (37)25 (44.6)
      Time of diagnosis

      6–10 years
      6 (5.6)3 (5.4)
      Time of diagnosis

      >10 years
      1 (0.9)0 (0.0)
      Anxiety21 (19.4)2 (3.6)<0.001
      Depression23 (21.3)4 (7.1)<0.001
      Pain score >435 (32.4)1 (1.8)<0.001
      Alcoholics4 (3.7)2 (3.6)1.000
      Smoking5 (4.6)4 (7.1)0.758
      Use of caffeinated drinks27 (25)12 (21.4)0.610
      Cough28 (25.9)16 (28.6)0.717
      Dyspnoea37 (34.3)8 (14.3)0.007
      Acidity21 (19.4)10 (17.9)0.806
      Surgery16 (14.8)8 (14.3)0.928
      Metastasis46 (42.6)22 (39.3)0.406
      Hypertension48 (44.4)15 (26.8)0.027
      Diabetes mellitus42 (38.9)10 (17.9)0.006
      Dyslipidemia17 (15.7)2 (3.6)0.040
      Hypertension was found to be the most prevalent co-morbidity in the sample population (44.4%), followed by diabetes mellitus and dyslipidemia. These co-morbidities were found to have a significant relationship with insomnia in our study [Table 2].
      • c)
        Therapy
      Chemotherapy was the most common treatment modality, with 64 insomniacs (59.3%) and 23 (41.1%) of the normal sleepers receiving it. Radiation was the second most common therapy received by the sample population (24 patients, 22.2%), while it was the third most common in normal sleepers (four patients, 7.1%). Both chemotherapy (P = 0.027) and radiation therapy (P = 0.015) were found to have a significant relationship with insomnia [Table 2].
      • d)
        Cancer
      The most common type of cancer in the insomnia population (33.3%) was breast cancer, followed by gastrointestinal (19.4%), lung (14.8%), and gynecological malignancy (10.2%). Also, 42.6% of the patients were in stage IV of cancer, and 33.3% were in stage III. Patients whose cancer was diagnosed <1 year prior to the study presented the highest percentage of insomniacs (56.5%). However, there was no significant relationship with cancer type, cancer stage and time from diagnosis of cancer [Table 2].
      • e)
        Other factors
      The mean anxiety, depression, and pain scores were 7.60 ± 4.09, 7.50 ± 4.07, and 2.51 ± 2.78, respectively. We found a significant influence of anxiety, depression, and pain on insomnia (P < 0.001 for all three parameters). More patients in the insomnia group experienced breathing difficulty at night (34.3%; P = 0.007) relative to patients without insomnia (14.3%). Breathing difficulty was especially prevalent in patients with lung cancer. However, insomnia did not appear to be significantly correlated with coughing, acidity, alcohol consumption, smoking, caffeine consumption, metastasis, or surgery [Table 2].

      5. Discussion

      The results elucidate the fact that a significant proportion of patients with cancer had sleep problems (65.9%). On average, more than 50% of our patients were poor sleepers with a mean PSQI global score of 9.12 ± 5.38. A large proportion of the included patients were females, but we did not find any significant correlation between female gender and insomnia—however, a meta-analysis by Zhang and Wing (2006)
      • Zhang B.
      • Wing Y.-K.
      Sex differences in insomnia: a meta-analysis.
      confirmed a female predisposition for insomnia. Also, more than half of females in the present study had already attained menopause. Terauchi et al. (2012)
      • Terauchi M.
      • Hiramitsu S.
      • Akiyoshi M.
      • et al.
      Associations between anxiety, depression and insomnia in peri- and post-menopausal women.
      affirmed that post-menopausal women suffer from a higher level of depression and anxiety when compared to pre-menopausal women.
      We studied the effect of anxiety and depression on insomnia and found a significant correlation between them. This was in agreement with a study by Taylor et al. (2005)
      • Taylor D.J.
      • Lichstein K.L.
      • Durrence H.H.
      • Reidel B.W.
      • Bush A.J.
      Epidemiology of insomnia, depression, and anxiety.
      that revealed that insomniacs were 9.82 times more prone to have clinically considerable depression and 17.35 times more susceptible to anxiety when compared to normal sleepers. Pain was one of the major factors contributing to insomnia. This was in line with a study conducted by Grond et al. (1994)
      • Grond S.
      • Zech D.
      • Diefenbach C.
      • Bischoff A.
      Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic.
      that showed that patients experiencing very severe or maximal pain complained more frequently of insomnia than other patients.
      We found that significantly more patients in the insomnia group were experiencing breathing difficulty at night relative to patients without insomnia. Breathing difficulty was more prevalent in patients with lung cancer. Hence, we assumed that breathing difficulty was related to lung cancer, which may have contributed to insomnia. The findings of the present study confirm an observation reported earlier by Hartz et al. (2007).
      • Hartz A.J.
      • Daly J.M.
      • Kohatsu N.D.
      • Stromquist A.M.
      • Jogerst G.J.
      • Kukoyi O.A.
      Risk factors for insomnia in a rural population.
      Another reason for the breathing difficulty may be season-related.
      In our study, hypertension was found to be a major risk factor for insomnia among co-morbidities, which was on par with the study by Palagini et al. (2013),
      • Palagini L.
      • Bruno R.M.
      • Gemignani A.
      • Baglioni C.
      • Ghiadoni L.
      • Riemann D.
      Sleep loss and hypertension: a systematic review.
      who found that perpetual insomnia, experimental sleep deprivation, and short sleep duration are related to high blood pressure and, subsequently, a high chance of developing hypertension.
      Diabetes mellitus was significantly associated with insomnia in our population. This may be a result of nocturnal hypoglycemia, nocturia, peripheral neuropathy, restless leg syndrome, and other factors associated with uncontrolled diabetes mellitus, which significantly tamper with the normal sleep of patients, thereby leading to poor quality of life as discussed by Surani et al. (2015).
      • Surani S.
      • Brito V.
      • Surani A.
      • Ghamande S.
      Effect of diabetes mellitus on sleep quality.
      Our study showed a correlation between dyslipidemia and insomnia, and we found a similar correlation in a study by Laugsand et al. (2011).
      • Laugsand L.E.
      • Vatten L.J.
      • Platou C.
      • Janszky I.
      Insomnia and the risk of acute myocardial infarction: a population study.
      The largest number of patients received chemotherapy, followed by radiation and hormonal therapy. There was a predominant association between chemotherapy and insomnia, and this result is supported by results published in an earlier study by Osoba et al. (1996–97).
      • Osoba D.
      • Zee B.
      • Warr D.
      • Kaizer L.
      • Latreille J.
      • Pater J.
      Quality of life studies in chemotherapy-induced emesis.
      ,
      • Osoba D.
      • Zee B.
      • Warr D.
      • Latreille J.
      • Kaizer L.
      • Pater J.
      Effect of postchemotherapy nausea and vomiting on health-related quality of life. The quality of life and symptom control committees of the national cancer Institute of Canada clinical trials group.
      Radiation therapy also showed a significant correlation with insomnia. Unlike the other two therapy types, hormonal therapy showed no significant correlation with insomnia.
      Also, our study found no significant correlation of insomnia with coughing, acidity, alcohol consumption, smoking, caffeine consumption, cancer type and stage, time since diagnosis, metastasis, or surgery.

      6. Conclusion

      Our results indicate that more than half the cancer population suffered from insomnia, and most of these cases are untreated. The majority of the patients refused to receive any sort of treatment, be it drugs or counselling. The severity of their disease forces them to ignore even severe problems like insomnia and instead consider them trivial. However, it is important to understand that sleep is essential to repairing the body and helping treatments bring about their desired effects. Risk factors such as breathing difficulty, hypertension, diabetes, dyslipidemia, radiotherapy, and chemotherapy had a significant association with insomnia.

      Funding

      Nil.

      CRediT authorship contribution statement

      Amrita Asok: Data curation, Writing – original draft, Formal analysis. Anagha C. C: Data curation, Writing – original draft, Formal analysis. Radhika T. K: Data curation, Writing – original draft, Formal analysis. Sreelakshmi Sreekumar: Data curation, Writing – original draft, Formal analysis. Merin Babu: Writing – review & editing. Uma Devi Padma: Conceptualization, Methodology, Software, Project administration, Visualization, Project administration. Keechilat Pavithran: Conceptualization, Methodology, Software, Project administration, Visualization, Project administration.

      Declaration of competing interest

      We wish to confirm that there are no known conflicts of interest associated with this publication.

      Acknowledgments

      We gratefully acknowledge the Amrita Institute of Medical Sciences and Research Centre and Amrita School of Pharmacy for the support and guidance.

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