Vol 5(1)

FREQUENCY OF DEPRESSIVE AND ANXIETY
SYMPTOMS AMONG PATIENTS ON INTER-
FERON AND PEGYLATED INTERFERON
Muhammad Waseem Shaikh1, Farah Ahmad2*, Gulnaz Shaikh1, Syed Hasan Danish2, Kirpal Das Makheja3,
Minhaj A Qidwai4
1Liaquat University Hospital Jamshoro, 2Department of Community Health Sciences , Ziauddin University 3Jinnah Postgraduate Medical Centers 4College of Physicians and Surgeons Pakistan
Background: Chronic Hepatitis C (CHC) is highly prevalent in Pakistan. Current standard treatment is Interferon alpha/
Peginterferon with oral ribavirin. Interferon therapy is associated with development & worsening of depressive symptoms in CHC patients and to determine the frequency of depressive and anxiety symptoms among patients on treatment with Methods: This cross sectional study was conducted at OPD of Liaquat University Hospital Hyderabad during a period of 4
months (from July2013 to October2013). A sample of 120 patients aged 18-60 years, either currently receiving interferon/ Pegasus treatment or had received that treatment during last 12 months was taken. Known cases of anxiety, depression and those suffering from other debilitating co morbid conditions like carcinoma & non-consenting were excluded. Ethical approval was taken from LUH ethical review committee. A Proforma was used to gather the data. The data collected were analyzed using SPSS version 20.0. Mean (±SD) were computed for quantitative variables. Categorical variables (such as gender and outcome variables i.e. anxiety and depressive symptoms) were measured in frequencies and percentag- es. Stratification was done with regard to age group & gender to see the impact of these on the outcome followed by application of chi-square test with P-value <0.05 taken significant.
Results: Total 120 patients were included in the study & 119 completed the questionnaire. Male patients were 55.5%.
Mean age of patients was 32.59 ± 8.56 years (Range: 16-56 years). Primary outcome i-e; frequency of depression & anxiety in patients on interferon were 77.3% & 70.6% respectively. (n=92) had depression. Frequency of depression of almost similar in both genders (77.3% in males & 77.4% in females; p value= 0.584), while anxiety was more in females than males (75% vs 68.2%; p value= 0.273). Both psychiatric symptoms increased with increasing age from 16-26 years to 47-56 years of age (p values = 0.432 & 0.736 respectively). Vast majority (86.6%) were treated with interferon while only 13.4% received the PEGylated interferon therapy. Patients treated with PEGylated interferon had less frequency of depression than those treated with interferon (62.5% vs 79.6%; p value= 0.131).
Conclusion: Depression and anxiety were found to be common in CHC patients who had been or are being treated with
antiviral treatment leading to increased risk of morbidity and mortality. Screening for risk of depression, proper education and timely treatment through anti-depressant followed by close monitoring is mandatory to achieve success in antiviral KEY WORDS: Hepatitis C, Depressive symptoms, Anxiety, Interferon alpha.
multiplying and causing further liver damage3. However, this treatment is often hampered by severe physical and Although about 3% of the world population is reported to psychiatric side effects2, 3. Interferon and Pegasus are be suffering from hepatitis C, the figures are not true repre- particularly notorious for causing depressive and anxiety sentative as many cases remain undiagnosed1. Large symptoms3, 4. Chronic Hepatitis C (CHC) patients may be numbers of patients suffering from chronic hepatitis C especially prone to develop interferon-induced depres- (CHC) are being treated with interferon, Pegasus (Pegylat- ed interferon α (pegIFN- α -2b, 1.5mg/kg, weekly, s.c.) and ribavirin (400 mg, b.d.)) because of significant advances in Anxiety and depressive symptoms emanating from overall improvement in the course of CHC2. Interferon, treatment with interferon and Pegasus contribute recommended treatment for CHC, is a manufactured enormously to impaired quality of life7 and are recognized drug that mimics the naturally occurring interferon as a major reason for treatment discontinuation, non-com- produced as part of the body's immune response to a viral pliance and dose reduction8,9. In the trial of Peginterferon infection. The aim of the drug is to prevent the virus from alfa-2a (Pegasus) and 2b plus ribavirin, 14% of patients had Corresponding Author: Farah Ahmad*
Pakistan Journal of Rehabilitation 2013 Volume 2 (Issue 1) PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2016, VOL. 5 (01) FREQUENCY OF DEPRESSIVE AND ANXIETY SYMPTOMS AMONG PATIENTS ON INTERFERON AND PEGYLATED INTERFERON to discontinue therapy. The most common adverse events ma & non-consenting were excluded. We used ICD-10 were influenza - like side effects such as fatigue, head- criteria to define depression i-e; a state of low mood and ache, fever and rigors, which occurred in more than half aversion to activity. It was labeled present if a patient had of the patients, and psychiatric side effects (depression, any 4 of the following symptoms; loss of interest and enjoy- irritability, and insomnia), which occurred in up to 31% of ment, reduced energy and decreased activity, reduced patients10. Depressive and anxiety symptoms may also concentration, reduced self-esteem, ideas of guilt and represent an independent risk factor for poor virologic unworthiness, pessimistic thoughts, ideas of self-harm/sui- response11. The most common psychiatric side effect of cidal thoughts, disturbed sleep, diminished appetite. We therapy, insomnia is present to some degree in 40% or so of used ICD-10 criteria to define anxiety also i-e; an unpleas- patients. Insomnia can lead to fatigue, headache, irritabil- ant state of inner turmoil, often accompanied by nervous ity, depression, and other side effects and thus worsening behavior. It was labeled present if a patient had any 4 of the situation. Another very common side effect, irritability is the following symptoms; fearful anticipation, irritability, reported in clinical trials in 30% or so of patients, but may restlessness, worrying thoughts, dry mouth, frequent or be present to a lesser degree in most patients12.
loose motions, constriction in the chest, palpitation, frequent or urgent micturition, tremor, headache, aching Significant depressive and anxiety symptoms occur in muscles, feeling of breathlessness, dizziness & night terror. about 20–60% of patients treated with interferon HCV infection5, 6, 13. Hauser et al., reported that depression was A Proforma comprising of the demographic and other found in 38% of patients after 12 weeks of treatment with relevant information and a check list of the depressive interferon5. A prospective study carried out in Pakistan and anxiety symptoms was used to gather the data after showed that 37% CHC patients were suffering from taking informed consent. The data collected was depression after 8 weeks of interferon therapy compared analyzed using computer packages SPSS (Statistical to 21% percent at baseline4.Further, suicidal ideation was Packages of Social Sciences) version 20.0. Mean and detected in all those patients who had severe depression. standard deviation (SD) were computed for quantitative In a study conducted at Shifa International Hospital, variables (such as age). Categorical variables (such as Islamabad from July 2011 to February 2012, depression gender and outcome variables i.e. anxiety and depressive was present in 27.6% of patients suffering from chronic symptoms) were measured in frequencies and percentag- hepatitis C, 58.6% of those suffering from chronic hepatitis es. Stratification was done with regard to age group and B, and among 37.8% of subjects suffering from neither of gender to see the impact of these variables on the the infections14. outcome. By using chi square test P-value <0.05 was considered as significant. Approval was taken from the Pakistan being one of the countries in the world where Ethical review committee of LUH Hyderabad.
prevalence rate of hepatitis is high (between 2.4% and 6.5%) and hence the use of interferon/Pegasus treatment is also on an increase15. Early detection of depressive symptoms may prompt the early treatment of these symp- toms as recent open trials also suggest that antidepressant treatment may reduce depression and anxiety during and after anti-viral therapy and thus help improve the quality Total 120 patients were included in the study & 119 of life of the patients16. Further in patients with uncontrolled completed the questionnaire regarding symptoms of depressive disorder treatment for CHC infection with depression and anxiety. Male patients were 55.5% (n=66) interferon/Pegasus is contraindicated17.
while females were 45.5% (n=53). Mean age of patients was 32.59 ± 8.56 years (Range: 16-56 years). Patients of Given the strong association between interferon/Pegasus age category 16-26 years were 27.7% (n=33), age catego- treatment and the psychiatric symptoms of depression ry 27-36 years were 43.7% (n=52), age category 37-46 and anxiety, this study is aimed at the detection of these years were 21.8% (n=26) and age category 47-56 were symptoms in the patients who are receiving or have received the antiviral therapy with interferon/Pegasus.
General characteristics are given in Table: 1. Patients referred by general practitioner were 37.8% (n=45), 15.1% (n=8) by consultant physician while the rest of patients were either brought by relatives/ themselves or by friends. Only 2.5% (n=3) were diagnosed as having hepatitis C in a hospital when they were admitted for some other illness The study was conducted at Outpatient department of and were suggested interferon therapy. It was noted that Liaquat University Hospital (LUH) Hyderabad during a 4 12.6% (n=15) patients had Hepatitis B, 73.1% (n= 87) had month period (from July2013 to October2013). Objectives Hepatitis C, while 14.3% (n=17) had both viral infections. of this cross sectional study were to determine the More than two thirds (68.1%) were diagnosed within last 6 frequency of depressive and anxiety symptoms among months and about 57.1% (n=68) had started their patients on interferon or Pegasus treatment and its relation treatment within previous 3 months while the rest of of age & gender with occurrence of symptoms. patients had started their therapy before this period. Psychiatric symptoms were more in those patients who Taking an estimated prevalence of depressive symptoms had received treatment before 3 months period than among patients on interferon therapy @ 20%8, the calcu- those who received it with three months period (p value= lated sample was approximated to 120. The study includ- ed patients aged 18-60 years, either currently receiving interferon/ Pegasus treatment or had received that It was further noted that about a quarter of patients treatment during last 12 months (records). Diagnosed (27.7%; n=33) had one or other psychiatric illness before cases of anxiety and depression and those diagnosed treatment with interferon and only half of these (n=17) had with other debilitating co morbid conditions like carcino- been treated for that psychiatric illness. PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2016, VOL. 5 (01) MUHAMMAD WASEEM SHAIKH, FARAH AHMAD, GULNAZ SHAIKH, SYED HASAN DANISH, KIRPAL DAS MAKHEJA, MINHAJ A QIDWAI Primary outcome of the study was frequency of depres- in females than males (75% vs. 68.2%; p value= 0.273). Age sion & anxiety in patients on interferon therapy and the of patients was seen to have an effect on frequency of results showed that 77.3% (n=92) had depression depression and anxiety in those treated with interferon the (presence of at least 4 symptoms of depression for >2 frequency of both depression and anxiety among patients weeks as per ICD-10) while patients having anxiety treated with interferon therapy. Both psychiatric symptoms (presence of at least 4 symptoms of anxiety for >2 weeks increased with increasing age from 16-26 years to 47-56 as per ICD-10) were 70.6% (n=84). years of age (p values = 0.432 & 0.736 respectively).
The study evaluated the role of gender and age in occur- It was important to note that vast majority i-e; 86.6% rence of psychiatric symptoms (depression & anxiety) as (n=103) were being treated with interferon while only additional outcomes in patients being treated with 13.4% (n=16) received the PEGylated interferon therapy. interferon therapy. It was noted that frequency of depres- Patients treated with PEGylated interferon had less sion was almost similar in both genders (77.3% in males & frequency of depression than those treated with interferon 77.4% in females; p value= 0.584), while anxiety was more (62.5% vs. 79.6%; p value= 0.131).
Table1: General characteristics of all patients
No formal education Mastrers or above Labour, farmer etc Pakistan Journal of Rehabilitation 2013 Volume 2 (Issue 1) PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2016, VOL. 5 (01) FREQUENCY OF DEPRESSIVE AND ANXIETY SYMPTOMS AMONG PATIENTS ON INTERFERON AND PEGYLATED INTERFERON Frequency of Depression among patients
treated with Interferon
Frequency of Anxiety among patients
treated with Interferon
No Anxiety
Figure 1: Frequency of depression & anxiety among patients treated with Interferon or
Pegasus treatment. P value= 0.584 & 0.273
PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2016, VOL. 5 (01) MUHAMMAD WASEEM SHAIKH, FARAH AHMAD, GULNAZ SHAIKH, SYED HASAN DANISH, KIRPAL DAS MAKHEJA, MINHAJ A QIDWAI Figure 2: Effect of gender on frequency of depression & anxiety among patients treated
with Interferon or Pegasus treatment. P value= 0.584 & 0.273
Frequency of depression and anxiety with increasing age
Figure 3: Effect of age on frequency of Depression & anxiety among patients treated
with Interferon or Pegasus treatment. P value= 0.432 & 0.735
Pakistan Journal of Rehabilitation 2013 Volume 2 (Issue 1) PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2016, VOL. 5 (01) FREQUENCY OF DEPRESSIVE AND ANXIETY SYMPTOMS AMONG PATIENTS ON INTERFERON AND PEGYLATED INTERFERON form of an epidemic and patients get HCV infection from mothers and till they become adult they develop CHC. According to the WHO statistics, there are 3 to 4 million newly infected cases of HCV each year and of these at Fried MW, et al.,13reported patients treated with Pegasus least 85% become chronically infected and about 70% had a lower incidence of depression than those treated develop CHC18. It is estimated that five out of every six with interferon (22% vs. 30%). Our study also found similar people HCV infected are undiagnosed and under-treat- results but the frequencies were higher. In our study ed and which causes further morbidity & mortality1, interferon treated patients had higher rates of depression 3-6,19while only 1 to 2% of HCV infected people are currently than those treated with Pegasus (79.6% vs 62.5%; p value= receiving internationally recognized and recommended therapy. Interferon & Pegasus prevent the virus from multiplying and causing further liver damage2,4,6 but are Other studies found that rate of suicidal ideation in CHC associated with psychiatric side effects such as depression pateints treated with IFNa was upto 26% of patients and anxiety7-9,11,20. These are two critical conditions which endorsed suicidal ideation & as much as 6.9% discontin- negatively affect patients' functional health, were found ued HCV treatment (pegylated IFN α) early, because of to be very strongly associated with decline in ability to work, self-perceived health, quality of life and well-being. These symptoms caused by antiviral therapy are usually The current study also evaluated and found that psychiat- reversed back to normal within 24 weeks of completion of ric symptoms were more in those patients who had antiviral therapy7,21.Interferon-alpha (IFN-alpha) induced received treatment before 3-6 months period (78-100%) depression is a major limitation for the treatment of chronic than those who received it with three months period (76%; hepatitis C, especially for patients with psychiatric p value= 0.092).
There is a debate that HCV patients having psychiatric The current study assessed the magnitude of burden of problems or prone to develop depression, should be depression and anxiety caused by interferon therapy and treated with interferon or not29. Use of prophylactic its variation as per gender and age. We found that anti-depressant is an answer to this problem. In a study depression & anxiety symptoms were quite common in Schaefer M, et al., 30 noted prophylactic use of antidepres- CHC patients on interferon therapy. More than three sants (like citalopram) as well as intensive psychiatric care fourths (77.3%) had depression while about 70.6% patients can spread most of patients (14% treated vs. 64% among had anxiety. Commonest depressive symptoms found in untreated with antidepressant; P value = 0.032) from our patients were depressed mood, loss of interest and developing major depression during antiviral treatment. enjoyment, reduced energy, decreased activity, We also noted that about 27% patients had psychiatric disturbed sleep &commonest anxiety symptoms were illness before treatment with interferon and only half of diminished appetite and irritability, worrying thoughts, dry these had been treated for that psychiatric illness. In those mouth, tremor, headache and aching muscles. Although who took treatment depression rate were much lesser male patients were slightly more (55%) than females (45%) than those who did not. (64% vs 79.4%; p value= 0.152) in our study, we noted that depression was almost equal in These results are backed by findings of review study which both genders (77.3% males & 77.4% females; p value= concluded that better treatment outcomes can be 0.584), while anxiety was more frequent in females than achieved by early identification of depression during HCV males (75% vs. 68.2%; p value= 0.273). The results were treatment and pre-emptive treatment approach31. Thus contrary to previous studies documenting male predomi- treatment for depression should be started early and psychosis managed with antipsychotics. Raison CL, et al.,13 Self-Rating Depression Scale (SDS) in 162 Although depression has been the focus of neuropsychiat- HCV-infected patients at baseline and after 4, 8, 12, and ric complications from interferon-alpha (IFNa), emerging 24 weeks of treatment with Pegylated IFN alpha-2b (PEG evidence has contributed to our understanding of IFNa-in- IFN) plus ribavirin found that 38.9% of patients exhibited duced suicidal ideation and attempts. In fact, suicidal moderate to severe depressive symptoms. A local study ideation has also commonly been identified among by Shakoor A, et al.,2 used major depressive episode of these patients and completed suicides have also been diagnostic and statistical manual (DSM-IV) reported that reported25. In our study the rate of suicidal thought was 39% patients had depression which was more common in 16.8%. These findings highlight the need to examine poten- female (44.4%) as compared to male (28.7%). Qureshi MO, tial therapeutic options for managing depression and et al.,14 reported that frequency of depression was 72.6% in anxiety during interferon therapy.
patients of CHC which is concordance with our results. The study used Hospital Anxiety and Depression Scale (HADS). It is utmost important that CHC patients which need antivi- The difference of frequency in literature is mainly due to ral therapy should be screened for psychiatric symptoms study population and the depression assessment scale before the start of interferon/Pegasus treatment. They used in the study. It is also important to discuss that many should be educated prior to treatment about a clear of contemporary studies document that the rate of description of likely side effects and their time course. depression among untreated patients with CHC range Besides at risk patients must be identified and pre-treated from 24% to 62% 22-24 and nearly two-thirds of depressed with antidepressant treatment. Mood and suicidal patients with CHC required antidepressant treatment22-24.
ideation should be monitored closely during interferon In our study the mean age of patients was 32.59 ± 8.56 years. Their ages ranged from 16-56 years, and majority of Our strength included diagnostic criteria based on the ICD them were in the 4th& 5th decades of life. Other studies guidelines. Data was collected by investigators them- have reported an elderly age (45-55 years)6,7, which may selves, Hospital cards were used as proof of treatment, be due to reason that in our country the CHC has taken limited number of studies has been conducted on this issue in Hyderabad. PAKISTAN JOURNAL OF MEDICINE AND DENTISTRY 2016, VOL. 5 (01) MUHAMMAD WASEEM SHAIKH, FARAH AHMAD, GULNAZ SHAIKH, SYED HASAN DANISH, KIRPAL DAS MAKHEJA, MINHAJ A QIDWAI 36: 812–8.
Our main limitation was the Temporality issue as it is cross 9. Schaefer M, Engelbrecht MA, Gut O, et al., Interferon sectional study, next time larger sample size can be taken alpha (IFNa) and psychiatric syndromes: a review. Pro into account by including more hospitals as only one Neuro- Psychopharml BiolPsychi 2002; 26: 731–46.
hospital was taken.
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effects like, depressive mood, GI disturbances, fatigue, 12. Interferon and Ribavirin Treatment Side Effects National anxiety, irritability, concentration difficulties, insomnia and Hepatitis C Program Office. http://www.hepatitis.va.gov- suicidal ideation etc. Depression and anxiety were found to be common in CHC patients who had been or are 13. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, being treated with antiviral treatment. This leads to Gonçales FL Jr, et al., Peginterferon alpha-2a plus ribavi- increased risk of morbidity and mortality. Screening for risk rin for chronic hepatitis C virus infection. N Engl J Med of depression, proper education regarding side effects and timely treatment through anti-depressant followed by 14. Qureshi MO ,Khokhar N, Shafqat F. Severity of depres- close monitoring is mandatory to achieve success in antivi- sion in hepatitis B and hepatitis C patients. J Col PhysSurg ral treatment.
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