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Depression and its Associated Factors with Multidrug-Resistant Tuberculosis
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Abstract
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Background: Both depression and Multi-drug resistant tuberculosis (MDR-TB) are global
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public health problems with substantial impact on human health. However, depressive state
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among MDR-TB patients has not been well investigated in Pakistan.
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Objective: To assess frequency of depression and to identify factors associated with depression
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among MDR-TB patients in our centre.
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Design: This was a cross sectional study conducted at programmatic management of drug
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resistant TB unit (PMDT), Lady Reading Hospital Peshawar (LRH), Pakistan.
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Result:
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A total of 289 patients were included in this study. Among total, 201(69.55%) of the study
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participants were classified depressed, 127 patients (63.18%) had mild depression, 61 patients
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(30.35%) had moderate depression, 13 patients (6.46%) were diagnosed with severe depression.
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Depression was found in 127 (43.9%) patients at the time of registration for MDR-TB treatment
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while at the end of 1st quarter 170 (58.8%) patients were depressed.
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Conclusion:
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Female, younger age, residence of urban area, longer duration of sickness, previous use of
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second line drugs (SLDs), any co-morbidity, poor socioeconomic status and poor outcome of
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previous TB treatment were associated with depression and were independent risk factors of
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depression.
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KEY WORDS: Depression; MDR-TB; PMDT; SLDs; Peshawar; Pakistan.
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1.
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The emergence of drugs resistance and in particular multidrug-resistant tuberculosis (MDR-TB),
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defined as resistance to isoniazid (INH) and rifampicin (RIF), has posed serious challenges in
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controlling TB.1,2 Compared to first-line anti TB therapy, compliance with MDR-TB treatment is
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considerably difficult because of its prolonged duration and frequent adverse effects of second-
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line drugs (SLDs).3
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Psychiatric complications are commonly associated with MDRTB both at baseline and due to
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SLD’s use. Baseline depression in MDRTB patients before the treatment is started was found in
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65% patients in a study in Pakistan.4 According to the findings of another study from Lima, Peru
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baseline depression was observed in 52.2% in MDR-TB patients. Reason stated for baseline
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depression in patients with MDR-TB include fear and guilt associated with infectious risk; the
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socio-economic and psychological burdens of living with a chronic, life-threatening illness;
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increased dependence on others; multiple treatment failures and being told in health centers that
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no further therapy was available; losing family members to the disease; and concomitant
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poverty.4 Social stigma, which may produce social isolation, diminished marriage prospects,
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limited social support, and may result in the denial of diagnosis and consequent rejection of
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treatment. 5
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The frequency of psychiatric disorders associated with MDR-TB treatment has been reported to
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be 21.3% patients,6 22% of MDR-TB patients. 7,8 Reported rate of depression in MDR-TB varies
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from 6.2% to 22%.3, 9-11 Several authors have described how these psychosocial factors
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complicate adherence to drug regimens, and emphasize the importance of attention to mental
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health in order to ensure positive treatment outcomes. 5
Introduction:
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Although most commonly psychiatric complications have been associated with cycloserine (CS)
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and INH, other drugs like ethionamide (ETO), ethambutol (EMB) and fluoroquinolones are also
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known to cause such complications. Severe psychiatric manifestations including hallucinations,
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anxiety, depression, behavioral disorders, and suicidal ideation and/or attempts have been
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reported to occur in 9.7–50% of individuals receiving CS. 12,13 Several case reports associate the
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use of ETO with occurrence of depression, anxiety, psychosis, and suicide. 3
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While adverse effects associated with MDR-TB therapy may be controlled effectively, some of
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these need special attention.14,15 Psychiatric problems such as depression can significantly affect
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patient quality of life, as well as physician’s approach toward MDR-TB therapy. Consequently
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effective management of depression is critical not only for desired patient outcome, but also for
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patient’s overall health and physician’s satisfaction while dealing with MDR-TB therapy.16
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Depression may also adversely affect the compliance to treatment and result in default which in
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turn may have serious consequences of treatment failure and further extension in drug resistance.
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Depression may be a very important negative factor to treatment adherence for patients on
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tuberculosis treatment 17,18 Despite the fact that Pakistan is among high prevalence country for
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MDR-TB, there is little data available about depression among MDR-TB patients, us providing
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justification for this study.
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All PMDT sites in Pakistan have a psychologist to address the issue of frequent psychiatric
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complications associated with MDR-TB treatment. In spite of the side effects the reported
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treatment success rate of MDR-TB patients is 78.7% in Pakistan. 19
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2. Methods
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2.1. Study Design
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This was a cross sectional study conducted to describe frequency of depression and other
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associated factors among MDR-TB patients.
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2.2. Subjects
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A total of 289 MDR-TB patients were included in the study, which were enrolled for treatment
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in this unit from January 2012 till December 2013.
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2.3 Data collection
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Patient interviews were conducted by one data collector using a structured questionnaire. The
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structured questionnaire was designed to assess socio-demographic factors such as marital status,
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socio-economic status, age, gender, duration of past treatment; weight, monthly income,
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residence, co-morbidity and patients contact status. All registered MDR-TB patients were
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assessed individually. After developing rapport with each patient, a semi-structured interview
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was conducted to collect demographic information. Psychological assessment was performed by
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a clinical psychologist using diagnostic and statistical manual of mental disorders, fourth edition
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(DSM-IV TR) criteria for depression and Hamilton Depression Rating scale. Every patient was
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assessed at the time of registration and at the end of 1st quarter.
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2.4 Tools
Hamilton Depression Rating Scale subsequent
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Hamilton depression rating scale (HAM-D) was used to assess depression among MDR-TB
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patients. The HAM-D scale consists of 20 questions according to the criteria of major depression
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as per the diagnostic and statistical manual of mental disorders, Fourth Edition, Text Revision
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(DSM-IV-TR). Total score range from 0 to 57 and indicate the severity of depression. In
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addition, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the
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interview and score the results. It’s a valid and reliable scale. Test-Retest reliability for Hamilton
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depression scale ranged from .65 to .98 according to a meta-analysis over a period of 49 years.20
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Whereas according to our study .84 is the reliability of this scale.
2.5 Ethical approval
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The study was approved by Research and Ethics Committee of the Postgraduate Medical
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Institute, Peshawar, Pakistan.
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2.6 Statistical analysis
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Following are the risk factors analyzed for association with depression: sex, age, marital status,
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positive history of past TB treatment and occurrence of any co-morbidity. Multivariable analysis
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was carried out using multiple regression model inclusive of all variables associated with a P
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value ≤ 0.05 or an odds ratio (OR) > 2.0 on univariate analysis.
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Reported P values were based on two-sided Fishers exact tests, or for continuous variables, t-
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tests or, if non-parametric, the Wilcoxon test. For binary variables, ORs with 95% confidence
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intervals (95%CIs) were also calculated.
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3. Results
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treated in the 2012 cohort at this center are described in Table 1. These patients were from
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different district of Khyber Pakhtunkhwa, FATA and Afghanistan, but maximum numbers of the
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patients (33%) were from district Peshawar, and a hundred and sixty three (56.0%) cases were
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from rural areas. Mean age of the study cases was 29.88 years ranging from 10 to 70 years;
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53.6% were female. Sixty percent of patients (60.2%) at the time of their treatment were married.
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Baseline weight of maximum number of patients was between 40-60 kg ranging from 16-78 kg
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with an average of 44 kg. Co-morbidity was found in Eighty five (29.4%) patients. Most of the
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study cases (61.2%) were of lower socio economic status with monthly income lower than ten
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thousand rupees monthly.
Total number of 289 patients was included in this study. Baseline characteristics of patients
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Depression was not found in 88(30.45%) patients, whereas 201(69.55%) of the study participants
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were classified as depressive on the HAM-D scale, 127 patients (63.18%) had mild depression,
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61 patients (30.35%) had moderate depression, 13 patients (6.46%) were diagnosed with severe
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depression. The prevalence of depression was assessed in each group, as well (Table 2).
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Depression was found in 127 (43.9%) patients at the time of registration for MDR-TB treatment
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while at the end of 1st quarter 170 (58.8%) patients were depressed. Among these 170 patients 96
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patients were those who depressed at start of the treatment on baseline.
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3.1 Factors associated with Depression
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Univariate analysis (Table 3) showed that patient with female sex (p=0.003), younger age (≤ 30
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years vs > 30 years) (p=0.028), residence of urban area (p=0.05), longer duration of sickness
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(p<0.001), previous use of second line tuberculosis drugs (SLDs) (p=0.05), any co-morbidity
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(p=0.001), poor socioeconomic status of the family (p=0.016) and poor outcome of previous TB
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treatment (p<0.001) were associated with depressive state.
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In a multivariate regression model, longer duration of illness (OR 0.156, 0.061-0.398, p < 0.001),
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residence of patient (OR 0.302, 0.116-0.781, p=0.014), and poor outcome of their past TB
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treatment (OR 0.109, 0.042-0.285, p < 0.021) were independent risk factors of depressive state of
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MDRTB patients during their treatment. This analysis showed that depression is found three
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times more in female patients as compared to male patients (OR 3.147, 1.189-8.329, p=0.021).
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Presence of any other co-morbidity increased the risk ten-fold (OR 10.521, 2.459-45.010,
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p=0.002) (Table 4). This model fit was based on non significant Hosmer and Lemeshow test
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(p=0.803) and overall percentage of 87.2% from classification table.
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4. DISCUSSION
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There is growing interest in psychiatric co-morbidities in population with physical illness and
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understandings to its unwanted consequences particularly poor adherence. 21 Primary aim of this
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study was to find out the rate of depression and factors responsible for it among MDR-TB
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patients. Frequency of depression observed in this study (87.5%) was much greater as compared
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with the prevalence in the general population of Pakistan (45.98%).
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greater as compared with 11% found by Aghanwa and colleague in Nigeria, 23 19% found in
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Turkey, 24 49% found by Natani and colleagues in India 25 and comparable with 80% found in
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This study finding is much
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hospitalized patients in Pakistan. 26 Compared with the previous reports in other countries,
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prevalence of depressive state among MDR-TB patients was relatively higher in the present
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study. A possible explanation justifying this result may include that MDR-TB treatment is of
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longer duration with extensive side effects as compared to first line drugs used for drug
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susceptible TB.
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Different studies have identified variety of factors associated with high rate of depressive state in
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MDR-TB patients including malnourishment, marital status of cohabiting, adverse effects of
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dugs, social disgrace, and the physiologic brunt of chronic illness, 17 inadequate social support. 27
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The present study showed that female patients (p<.01), younger age (≤ 30 years vs > 30 years)
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(p<.05), locality of urban areas (p<.05), longer duration of sickness (p<.001), previous use of
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SLDs (p<.05), any associated co-morbidity (p<.001), poor socio-economic status of family
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(p<.01) and poor outcome of previous TB treatment (p<.001) were associated with depressive
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state.
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Women are reported to have high prevalence, incidence and morbidity associated with
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depressive disorders. Our findings are consistent with other studies where women had higher
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level of depression than men, also observed by a study conducted in Pakistan. 8 The gender
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difference is likely to be due to a complex interaction between biological, psychological and
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socio-cultural vulnerabilities. 28 Female patients with MDR-TB in developing counties become
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lonely, are underestimated and socially stigmatized with consequent depression. 29 Gender
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depression is also associated with younger age. 26 In the present study all MDR-TB patient with
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age lower than 30 years, had experienced more episode of depression as compared to older age
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patients. Possible explanation for the stated reason is that as MDR-TB treatment is for longer
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duration, expensive, large number of drugs accompanied by wide variety of side effects, thus
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making young people more prone to loss in their self esteem and courage.30 Low maturity level
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cannot withstand such harsh situation of disease burden as well as social stigma hence leading
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towards significant depression as compared to old age.31
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An additional significant finding of the current study was positive association of depression with
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duration of sickness. Patients with longer period of illness experienced higher degree of
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depression. Reason may include hopelessness, sense of worthlessness, hospitalization, social
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stigmatization and loss of earning all these factors lead to self depreciation, conscious and
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unconscious fear of ailment and death. A positive correlation between disease duration and
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incidence of depression has also been observed in other studies. 32,33 Severity of depression was
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directly related to the duration and severity of disease and response to pharmacotherapy. 25 Our
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study showed positive relation of depression with past treatment outcome and previous use of
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SLDs. Patients with unsuccessful outcome suffer from more depression because of uncertainty of
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the outcome of the therapy, repeating the same medicines or further additions in therapy, use of
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SLDs and its known and already experienced side effects.34
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Although in Pakistan the treatment of drug susceptible and drug resistant TB is free of cost,35 the
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burden of poverty and its psychological consequences, in association with the stigma of MDR-
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TB, and its physical impact is likely to compound the stress leading to further deterioration of
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coping mechanisms. MDR-TB patients are physically as well as mentally compromised to be
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able to lead a productive life, so their socio-economics tend to deteriorate. Consequently they are
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unable to support their family resulting in loss of self esteem, and development of depressive
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disorders.36
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Depression is also associated with poor adherence to medication, and may be related to
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medication adherence in MDR-TB patients, although we could not assess the relationship in this
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study. Screening and follow-up for depression are recommended for MDR-TB patients, which
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could reduce the disease burden by increasing treatment adherence.17
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Baseline as well as ongoing monitoring of patient’s mental health status is very important as it
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may facilitate the health care professionals, patients and their family members in proper
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management of a patient’s condition during entire illness.
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Psychiatric co-morbidities are frequently associated with MDR-TB and their presence is not a
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contra-indications to MDR-TB treatment, as described by Vega et al.6 However, one should be
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cautious during the treatment of depressive symptoms in MDR-TB patients receiving a regimen
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inclusive of CS as it may be difficult to distinguish the drug-induced psychological problems 35
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and/or identification of pharmacological interactions between MDR-TB drugs and anti-
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depressants. Care should be individually tailored to help patients cope with the combined burden
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of depressive symptoms in addition to their illness of MDR-TB. 38
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Conclusion
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Depression during MDR-TB treatment needs particular attention. Health care professionals
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involved in management of MDR-TB patients should be properly skilled to execute proper
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mental health assessment tools, in particular at baseline, so that presence of depression can be
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identified on earlier basis. It is recommended to regularly monitor the mental health status of
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MDR-TB patients by skilled Clinical Psychologist/counselors, using simple, validated and cost-
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effective tools.
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ACKNOWLEDGEMENTS
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We acknowledge the outstanding contributions from the PMDT staff, National TB control
Programme Pakistan (NTP), Provincial TB Control Programme Khyber Pakhtunkhwa (PTP
KPK), Association for Community Development (ACD) and Lady Reading Hospital Peshawar
(LRH) in this programme.
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Author Contributions
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Conceived and designed the experiment: SM, Performed the experiments: MAK SM, Data
collection: SM NA, Data entry: MAK SM, Analyzed the data: MAK SM, Management of
patients: AJ AB MAK SM AK, Wrote the paper: SM MAK and AJ. Revised the manuscript: AJ
AB SM MAK MI IU.
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