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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 2  |  Issue : 1  |  Page : 14-19

Adverse drug reaction monitoring of antidepressants in the psychiatry out patient department at a tertiary care teaching hospital in India: A cross-sectional observational study


1 Department of Clinical and Experimental Pharmacology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
2 Department of Psychiatry, Medical College and Hospital, Kolkata, West Bengal, India

Date of Web Publication23-Jul-2015

Correspondence Address:
Dr. Sukanta Sen
Department Clinical and Experimental Pharmacology, Calcutta School of Tropical Medicine, 108 C R Avenue, Kolkata - 700 073, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2395-2555.161417

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  Abstract 

Background: Antidepressant drugs, though of great benefit in a range of psychiatric disorders, are associated with a wide range of potential adverse effects. There is growing concern among the healthcare personnel to assess these adverse drug reactions (ADRs) of newer psychotropic drugs, which have an impact on long-term compliance and achieving successful treatment. The present study was thus designed to monitor and analyze the pattern of occurrence of ADRs to antidepressant medications in Outpatient Department (OPD) of a tertiary-care hospital. Materials and Methods: A cross-sectional observational clinical study was carried out in the OPD of Psychiatry in Medical College, Kolkata. A total of 190 patients who received antidepressants were studied. 5-8 consecutive previously diagnosed depression patients attending follow-up per day, were screened for suspected ADRs, 2 days (one male OPD and one female OPD) in a week, over 6 months (October 2013 to March 2014). Adverse event history, medication history and other relevant details were captured in a format as adopted in the Pharmacovigilance Programme of India (PvPI). Causality of ADR was assessed by Naranjo's ADR probability scale. The severity of each reported ADR was assessed using Hartwig and Siegel Scale. All the statistical analysis was done by using SPSS-version 20 (SPSS Inc). Results: A total of 190 patients were screened for the study of which males and females represented 43.68% and 56.31% of the cases respectively. The age-group presenting with maximum depressive problems was found to be 30-39 years. A total of 481 ADRs were noted of which dry mouth was the commonest, closely followed by nausea and tremor. Out of 130 ADRs assessed for causality, 89.23% of the ADR cases, were found to be 'probable', while 10.77% were found to be 'possible'. According to Hartwig and Siegel's Scale 83.99% of the cases were found to be mild, 14.97% moderate and 1.04% severe. Conclusion: The study enables to obtain information on the incidence and pattern of adverse drug reactions associated with antidepressants in the local population thereby reducing its occurrence and protecting the user population from avoidable harm.

Keywords: Adverse drug reactions, antidepressants, causality assessment scale, pharmacovigilance, severity assessment scale


How to cite this article:
Mukherjee S, Sen S, Chatterjee SS, Era N, Ghosal M, Tripathi SK. Adverse drug reaction monitoring of antidepressants in the psychiatry out patient department at a tertiary care teaching hospital in India: A cross-sectional observational study. Eur J Psychol Educ Studies 2015;2:14-9

How to cite this URL:
Mukherjee S, Sen S, Chatterjee SS, Era N, Ghosal M, Tripathi SK. Adverse drug reaction monitoring of antidepressants in the psychiatry out patient department at a tertiary care teaching hospital in India: A cross-sectional observational study. Eur J Psychol Educ Studies [serial online] 2015 [cited 2019 May 20];2:14-9. Available from: http://www.ejpes.org/text.asp?2015/2/1/14/161417


  Introduction Top


Depression is the most common of the affective (mood) disorders; it may range from a very mild condition, bordering on normality, to severe (psychotic) depression accompanied by hallucinations and delusions. World Health Organisation (WHO) estimates suggest that depression is common in all regions of the world. A recent study supported by WHO revealed that around 5% of people in the community had depression during the last year. Depression is a significant contributor to the global burden of disease and affects people in all communities across the world. Today, depression is estimated to affect 350 million people. The World Mental Health Survey conducted in 17 countries found that on average about 1 in 20 people reported having an episode of depression in the previous year. Depressive disorders often start at a young age; they reduce people's functioning and often are recurring. For these reasons, depression is the leading cause of disability worldwide in terms of total years lost due to disability. [1] Over-diagnosis of depression may be common, because while the prevalence of major depressive disorder has remained unchanged, its diagnosis has doubled in 20 years. Depression is more likely over-diagnosed than under-diagnosed in primary care, resulting in patients without evidence of major depressive disorder being prescribed medications. [2] The elderly may be at more risk of over-diagnosis. [3]

The expanding and challenging field of psychopharmacology is constantly seeking new and improved drugs to treat psychiatric disorders. There are number of adverse drug reactions associated with these medications, which leads to noncompliance and thereby discontinuation of the therapy. Up to 70% of patients taking antidepressants are noncompliant, as a result of either missed doses or premature discontinuation. [4] There is growing concern among the health care personnel to assess the adverse drug reactions (ADRs) of newer psychotropic drugs, which have an impact on long-term compliance and achieving successful treatment. In India, Pharmacovigilance activities are still in the nascent stage and data of ADRs particularly related to newer antidepressant drugs need to be strengthened. Extensive PubMed search revealed that only two dedicated ADR monitoring study on patients receiving antidepressants drugs were done in Indian populations. [5],[6]

As there is only limited data available regarding the safety of antidepressants in the local population (Eastern part of India), this study was intended to monitor and analyze the pattern of occurrence of ADRs to antidepressant medications in OPD of a tertiary care hospital.


  Materials and Methods Top


A cross-sectional observational clinical study was carried out in the OPD Psychiatry in Medical College, Kolkata. A total of 190 patients who received antidepressants were studied. 5-8 consecutive previously diagnosed depression patients attending follow-up per day, were screened for suspected ADRs, 2 days (one male OPD and one female OPD) in a week, over 6 months (October 2013 to March 2014). Permission from the Institutional Ethics Committee was obtained before starting research work. Antidepressant medication received by the subjects in our hospital set-up were ascertained by noting down the type of disease, drug doses and frequency of the drugs, strength of antidepressant, the duration of the treatment, etc., in the prescribed proforma. Any change of drugs or the dosing schedule of the drug in subsequent visits of patients to the hospital was recorded. Adverse event history, medication history and other relevant details was captured in a format as adopted in the Pharmacovigilance Programme of India (PvPI). [7] Causality was assessed by Naranjo's Adverse Drug Reaction Probability Scale. [8] The severity of each reported ADR was assessed using Hartwig and Siegel Scale. [9] Subjects and their accompanying family members were interviewed by pre-structured questionnaire, and past prescriptions and case notes, where available, were reviewed and recorded. A senior psychiatrist was available for consultation in the event of any difficulty. All decisions relating to management of the patient including drugs and investigations were taken by the treating physician only. Investigator did not interfere in the management of patient and only observed the proceedings.

Inclusion criteria

  • Subjects who were suffering from depressive disorder and under only antidepressant medication attended the Psychiatry O. P. D. and willing to participate
  • Patients from all age groups and both the sexes were included
  • Pregnant ladies who were suffering from depressive disorders
  • Those who understood the purpose of the study and were ready to provide information regarding their health status and those who signed an informed consent document.


Exclusion criteria

  • Subjects not agreeing to participate
  • Those who had a history of substance abuse
  • Those who were judged clinically to be at a suicidal risk (too serious to be included in the study)
  • Suffering from any serious disease such as unstable coronary heart disease, heart failure, advanced kidney or liver failure
  • Any condition resulting in severe learning disability (e. g., brain injury) or
  • Those unable to comprehend for other reasons will be excluded from the study.



  Results Top


A total 190 patients were screened and each was suspected of having multiple ADRs. Total of 481 ADRs were noted. Out of 190 patients, males represented 43.68% (N = 83) of the cases, while females represented 56.31% (N = 107) of the cases. In our study, we found that the age group presenting with maximum depressive problems was 30-39 years (36.84%, N = 70), closely followed by age group 20-29 years (30.53% N = 58) [Table 1].
Table 1: Demographic data


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Out of 190 patients monitored, major depression was the most common disorder encountered (53.68%), followed by anxiety (25.79%) [Table 2].
Table 2: Diagnostic profile of patients who attended the Psychiatric OPD


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One hundred and three patients (54.21%) among the 190 studied received SSRIs while 32 (16.84%) received TCAs and 7 (3.68%) received newer antidepressants (SNRI/NDRI). Combination of SSRI and TCA were prescribed in 20 (10.53%) while combination of SSRI and NDRI were prescribed in 11 (5.79%). Combination of TCA and TeCA were prescribed in four (2.10%) while combination of SSRI and TeCA were prescribed in 7 (3.68%). Three (1.58%) received SNRI and TeCA in combination [Table 3].
Table 3: Utilization pattern of different groups of antidepressant drugs


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Among 142 patients who received monotherapy, 48 received escitalopram, 32 received amitriptyline, 22 received fluoxetine, 16 received sertraline, seven received venlafaxine, two received paroxetine and three received mirtazapine.

Similarly out of 48 patients who received polytherapy with two different groups of antidepressants, 10 received amitriptyline and sertraline; six received escitalopram and amitriptyline; six received escitalopram and bupropion; five received fluoxetine and bupropion; four received amitriptyline and mirtazapine; four received fluoxetine and mirtazapine; four received amitriptyline and fluoxetine; three received paroxetine and fluoxetine; three received venlafaxine and mirtazapine while another three received escitalopram and mirtazapine [Table 4].
Table 4: Prescribing pattern of individual & combination antidepressant drugs


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It is observed that, the most frequently prescribed antidepressant was escitalopram (in 48 cases, 25.26%); followed by amitriptyline (in 32 cases, 16.84%) and the most frequently prescribed newer antidepressant was venlafaxine (in seven cases, 3.68%). The most frequently prescribed combination therapy was that of amitriptyline and sertraline (10, 5.26%) in the study population.

Four-hundred and eighty-one different kinds of treatment emergent ADRs were encountered in the patients. Dry mouth was the commonest ADR noted (6.44%), closely followed by nausea (6.03%) and tremor (5.82%) [Table 5].
Table 5: Frequency of various ADRs observed among 190 patients


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Out of 190 patients monitored, 80 patients were assessed for causality. Causality has been assessed for a total of 130 ADR cases out of 672 cases by Naranjo's algorithm. [5] 89.23% of the ADR cases (N = 116), were found to be 'probable', whereas 10.77% (N = 14) were found to be 'possible'. No cases could be labeled 'certain' as rechallenge was not attempted by the attending physician once the drug was withdrawn [Figure 1].
Figure 1: Causality assessment using Naranjo's Algorithm

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Severity of 481 ADR has been assessed with the help of Hartwig and Siegel's Scale. [6] An estimate of 83.99% (N = 404) of the cases were found to be mild, whereas 14.97% cases were found to be moderate (N = 72). 1.04% cases (N = 5) were found to be severe [Table 6].
Table 6: Severity assessment using Hartwig and Siegel's Scale


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Some interesting ADRs were noted during the course of study. Three cases of suicidal ideations induced by chronic use of selective serotonin reuptake inhibitors (SSRI) were noted, which were managed by discontinuation of the precipitating drug by the concerned physician. One case of escitalopram induced bruxism was noted during the tenure of our study which was managed by initial dosage reduction followed by complete dechallenge and subsequent prescribing of buspirone. Another case of drug induced speech problem was encountered during our study period.


  Discussion Top


The present study had reported the incidence and attempted to profile suspected ADRs associated with antidepressant medications in a psychiatry OPD setting in a tertiary-care teaching hospital in India. Demographic analysis conferred that females showed significantly higher morbidity compared to males (P = 0.365). Age was found to be an important criterion in the fact that patients belonging to age group of 30-39 years showed higher morbidity followed by 20-29 years. A study by Solanke et al., [10] and S Mishra et al., [6] reported similar findings.

Analysis of the diagnostic pattern suggested that major depression was the most common psychiatric illness encountered followed by anxiety and obsessive compulsive disorder respectively. This analysis is useful to find the precipitating cause for the prescribing medication and to judge the rationality for such prescribing pattern.

Drug utilization assessment is a powerful exploratory tool to ascertain the role of drugs in the society which refers to the marketing, distribution, prescription, and use of drugs with special emphasis on the medical, social and economic consequences. [11] Drug utilization pattern suggested that out of 190 patients monitored, monotherapy was practiced in 74.74% cases where selective serotonin was prescribed in 54.21% cases, thus being the most commonly prescribed antidepressant medication in our OPD. This data was followed by tricyclic antidepressants (TCA) being prescribed in 16.84% of the cases. Polytherapy was practiced in 25.26% of the study population where combination therapy of amitriptyline and sertraline (N = 10, 5.26%) was found to be the most frequently prescribed one in our study population. We can say that polypharmacy was avoided, as no patients were prescribed four or more than fore drugs. Polypharmacy can lead to poor compliance, drug interactions, adverse drug reactions, under-use of effective treatments and medication errors. [12],[13]

The value of medical audits for generating and testing hypotheses on inappropriate prescribing has resulted in educational interventions to improve prescribing patterns. [14],[15]

A total of 481 ADRs were noted out of 190 patients monitored with each patient presenting with at least two ADRs or sometimes more than that in average. Among the various ADR monitored, dry mouth (6.44%) was found to be the most common, followed by nausea (6.03%) and tremor (5.82%).

ADR affecting nervous system were dry mouth, sweating, headache, nervousness, anxiety, dizziness, sedation, tremor, drowsiness etc., among them, dry mouth was found to be most commonly encountered reaction, which was found mostly associated with TCA and SSRI drug combinations. ADR affecting gastrointestinal system included nausea, diarrhea, constipation, epigastric disorder, vomiting, abdominal pain, flatulence, dyspepsia etc. Psychiatric system associated ADR such as insomnia; somnolence, delirium, impaired concentration etc., have been studied for their incidence pattern with the prescribed drug regime. General ADRs such as fatigue, weight gain, blurred vision etc., was found to be quite common in the study population.

No fatalities were reported. Out of 190 patients monitored, 80 patients who presented with a total of 130 ADRs could be assessed for causality using Naranjo's scale-for 116 of those ADRs, the causality was 'probable'; for the rest 14, it was 'possible'. Our study had no 'certain' cases as rechallenge was not attempted by the attending physician, once a drug was withdrawn. This is in contrast to a Brazilian study conducted in 2001, where 24 cases were found to be 'definite' after rechallenge was attempted. [16]

Severity of the adverse drug reactions were assessed for a total of 481 ADR with the help of Hartwig and Siegel's Scale. 83.99% (N = 404) of the cases were found to be mild, while 14.97% cases were found to be moderate (N = 72). Only five of all the ADRs (1.04%) were severe in nature; three were 'suicidal ideation', and two were speech problems.

Limitations of present study and implications

Our study had certain limitations. It was a small sample sized cross sectional study. Being an OPD based study; it is quite possible that we had missed ADRs that were transient or too mild to have inconvenienced the patient to an extent sufficient to report to the doctor on the next hospital visit. We had not taken diet and other confounding factors into account which might have influenced weight changes. There was no access to therapeutic drug monitoring (TDM) for any drug in the hospital setting. Being a cross-sectional study, we could not assess the causality for the entire study population but only those who turned up for the review. Being a government set up, no other detailed investigations could be ordered apart from routine laboratory investigations and hematological tests. Moreover the study was conducted only for a short period at a single centre with a small sample size.

But at the same time, by knowing the incidence, the demographic profile and the causative agents of the various ADRs, many common ADRs which are caused by antidepressants can be avoided. This study represented the adverse effects scenario in the patients on antidepressants of eastern India and it provided the baseline data for its comparison with other similar studies which were done in different parts of the country. Awareness should be created among the physicians as well as the patients regarding the various ADRs which are caused by antidepressants, so that the morbidity can be reduced.


  Conclusion Top


India rates below 1% in terms of ADR reporting against the world's rate of 5%. [17] In India there are very few active ADRs monitoring centers and a lot of effort is required in order to collect ADR data which may generate from safety surveillance of billions of therapeutically active substances either alone or in combinations. Most medicines will only have been tested for short-term safety and efficacy on a limited number of carefully selected individuals. Therefore, it is important that the use of these medicines is monitored for their ongoing effectiveness and safety. Very few studies have described patient characteristics and treatment patterns associated with long-term use of the drugs. Our study enables to obtain information on the incidence and pattern of adverse drug reactions associated with antidepressants in the local population that allows opportunity for education to the clinicians to reduce its occurrence thereby protecting the user population from avoidable harm. Pharmacovigilance thus may be enforced in our country for better and safe use of drugs. Our ability to anticipate and present such ADR's can be facilitated by the establishment of standardized approaches and active reporting of suspected ADR's by all health care professionals.

 
  References Top

1.
World Health Organization. Mental health. Fact sheet on Depression. Depression - A hidden burden. Available from: http://www.who.int/mental_health/management/depression/flyer_depression_2012.pdf [Last accessed on 2014 Apr 24].  Back to cited text no. 1
    
2.
Dowrick C, Frances A. Medicalising unhappiness: New classification of depression risks more patients being put on drug treatment from which they will not benefit. BMJ 2013;347:f7140.  Back to cited text no. 2
    
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Mojtabai R. Clinician-identified depression in community settings: Concordance with structured-interview diagnoses. Psychother Psychosom 2013;82:161-9.  Back to cited text no. 3
    
4.
Richelson E. Interaction of antidepressants with neurotransmitter transporters and receptors and their clinical relevance. J Clin Psychiatry 2003;64:5-12.  Back to cited text no. 4
    
5.
Lucca JM, Madhan R, Gurumurthy P, Dushad R. A prospective observational study to evaluate safety reporting of antidepressants at a tertiary care hospital in India. Indian J Pharmacol 2014;46:543-6.  Back to cited text no. 5
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Mishra S, Swain TR, Mohanty M. Adverse drug reaction monitoring of antidepressants in the psychiatry outpatients department of a tertiary care teaching hospital. J Clin Diagn Res 2013;7:1131-4.  Back to cited text no. 6
    
7.
Suspected adverse drug reaction reporting form-CDSCO. Available from: http://www.cdsco.nic.in/ADR_form_PvPI.pdf [Last accessed on 2013 Aug 11].  Back to cited text no. 7
    
8.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 8
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Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229-32.  Back to cited text no. 9
    
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Solanke B, Mahatme MS, Dakhale G, Hiware S, Shrivastava M, Waradkar P. Adverse drug reaction profile at psychiatry out-patient department of a tertiary referral centre in Central India. Int J Basic Clin Pharmacol 2013;2:341-3.  Back to cited text no. 10
    
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World Health Organization. Introduction to drug utilization research. WHO International Working Group for Drug Statistics Methodology, WHO Collaborating Centre for Drug Statistics Methodology, WHO Collaborating Centre for Drug Utilization Research and Clinical Pharmacological Services. Geneva: World Health Organization. 2003. p. 6-48.  Back to cited text no. 11
    
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Nobili A, Garattini S, Mannucci P. Multiple diseases and polypharmacy in the elderly: Challenges for the internist of the third millennium. J Comorbidity 2011;1:28-44.  Back to cited text no. 12
    
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Bushardt RL, Massey EB, Simpson TW, Ariail JC, Simpson KN. Polypharmacy: Misleading, but manageable. Clin Interv Aging 2008;3:383-9.  Back to cited text no. 13
    
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Hurley SF, Mc Neil JJ, Jolley DJ, Harvey R. Linking prescription and patient-identifying data: A pilot study. Med J Aust 1992;156:383-6.  Back to cited text no. 14
    
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Klein LE, Charache P, Johannes RS. Effect of physician tutorials on prescribing patterns of graduate physicians. J Med Educ 1981;56:504-11.  Back to cited text no. 15
[PUBMED]    
16.
Carlini AE, Nappo AS. The pharmacovigilance of psychoactive agents in Brazil. Rev Bras Psiquiatr 2003;25:200-5.  Back to cited text no. 16
    
17.
Prakash S. Pharmacovigilance in India. Indian J Pharmacol 2007;39:123-3.  Back to cited text no. 17
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