Indian Journal of Pharmacology Home 

[Download PDF]
Year : 2014  |  Volume : 46  |  Issue : 5  |  Page : 543--546

A prospective observational study to evaluate safety reporting of antidepressants at a tertiary care hospital in India

Jisha M Lucca1, Ramesh Madhan1, Parthasarathi Gurumurthy1, Ram Dushad2,  
1 Department of Pharmacy Practice, Jagadguru Sri Shivarathreeshwara College of Pharmacy, Jagadguru Sri Shivarathreeshwara University, Mysore, Karnataka, India
2 Department of Psychiatry, Jagadguru Sri Shivarathreeshwara Hospital, Mysore, Karnataka, India

Correspondence Address:
Ramesh Madhan
Department of Pharmacy Practice, Jagadguru Sri Shivarathreeshwara College of Pharmacy, Jagadguru Sri Shivarathreeshwara University, Mysore, Karnataka


Objective: This prospective observational study was carried out to identify the prevalence and Severity of ADRs of antidepressant in a tertiary care teaching hospital. Materials and Methods: Patients prescribed with at least one antidepressant were randomly selected and monitored for adverse drug reactions (ADRs), irrespective of their age and gender. Results: Of the 401 patients who received antidepressants, 170 patients (42.39%) experienced 204 ADRs. Selective serotonin receptor inhibitors (SSRIs) [110 (53.92)] was the most common therapeutic class of drugs associated with ADRs. Gastrointestinal system [54 (26.47)] was most commonly affected system organ class. Dry mouth (n = 30) and diaphoresis (n = 21) were the most frequently reported ADRs. As assessed by the World Health organization (WHO) probability scale, 61% of the ADRs were «SQ»probable«SQ» causality. Among all the ADRs, 22.54% (46) were preventable. Majority of the ADRs [(n = 184) 90.17%] were «SQ»mild«SQ» in their severity. Conclusion: In this study, incidence of adverse reaction to antidepressants was 42.3% were the most comman SSRI inplicated drug group for the ADRs.

How to cite this article:
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;46:543-546

How to cite this URL:
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 [serial online] 2014 [cited 2022 May 24 ];46:543-546
Available from:

Full Text


Depression is one of the most widespread illnesses, often co-existing with other serious illnesses like cancer, cardiovascular disorders and chronic kidney disorders. [1],[2] Medications are the mainstay of treatment for moderate to severe depression, often combined with psychotherapy. [2] Although currently available the antidepressant medications are effective but are not devoid of adverse effects. [3],[4] The prevalence of adverse drug reactions (ADRs) in the psychiatric patients varies from 17.25% to 60.7%. [5],[6],[7] The rate of ADRs due to psychiatric hospitalization has been reported to be 4.2 events per hundred admissions. Moreover 10/1000 patient days in psychiatric hospital are due to ADRs. [8] Several studies show that antidepressants and antipsychotics are most frequently associated with ADRs, which accounts for approximately 90% of all ADRs in the psychiatry department. [5],[8],[9] Benign and transient side effects are more common than dangerous or irreversible effects, especially with the newer antidepressant drugs. [10] ADRs due to antidepressants decreases adherence and delay recovery and may also cause treatment failure. [11],[12] In context of increased number of newer antidepressants in the market and the use of different class of antidepressants in the psychiatric patients is important to assess the safety profile of antidepressants. As there is only limited data available regarding the safety of psychotropic agents especially on antidepressants in the local population, this study is intended to assess the incidence and pattern of ADRs to antidepressants in local population.

 Materials and Methods

This prospective observational study was undertaken in the psychiatry department of a tertiary care hospital in south India over a period of one year from April 2012 to March 2013. The study protocol was reviewed and approved by Institutional Ethics Committee. Consent was taken from all the patients enrolling into the study.

Study Patients

Patients of any age and either gender who presented with psychiatric illness as diagnosed by ICD-10 and were receiving at least one antidepressant were included in the study. Patients who presented to psychiatry services were recruited and those seen consultation liaison were not included. Patients who are taking fixed drug combination of antidepressants with any other medication; patients taking antidepressants for neurological disorders other than Alzheimer's disease and vascular dementia were excluded.


All patients who visited to the psychiatric department were reviewed by a psychiatry clinical pharmacist and those patients who met the study criteria were enrolled. Review was done to identify any new symptoms that were not present prior to the start of the drug therapy. Also worsening of existing symptoms and any change in the laboratory values compared with the baseline values were evaluated to detect an ADR. Inpatients were monitored for ADR throughout their hospital stay while outpatients were monitored during their subsequent visits to the outpatient department over a period of one year. The World Health Organization (WHO) definition of an ADR was adopted. Objective findings of ADRs were identified from laboratory reports, whereas subjective markers of ADRs were identified from the reviews of clinicians' and nurses' notes and also discussion with the patient and clinicians. Both intensive and spontaneous reporting systems of ADR monitoring were adopted.

Drugs received and ADRs experienced by the study patients were recorded and coded using WHO Anatomical Therapeutic and Chemical (WHO-ATC) classification and WHO-Adverse Reaction Terminologies (WHO-ART) respectively. Where an adverse event was identified/reported, causality of suspected ADR was established using the WHO probability scale. Preventability and severity of ADRs were assessed by using the modified Schumock and Thornton criteria and Modified Hartwig and Siegel scale respectively. Predictability of an ADR was assessed based on incidence of reported ADR and taking the history of previous drug allergy status. The overall prevalence of ADRs was determined by taking the ratio of total number of patients who experienced ADRs to the total number of patients included in the study.


Of the 653 patients reviewed, 401 (61.4%) patients received at least one antidepressant. Among the 401 patients taking antidepressants, 299 (74.56%) were outpatients and 102 (25.43%) were inpatients. A total of 204 ADRs were identified from 170 patients giving an overall incidence rate of 42.39%. Average number of ADR per patient was 1.2. Median age of the study population was 35.6 years (range: 8 to 72 years), whereas the median age of patients without ADRs was 36.5 years (range: 13 to 84 years). Gender distributions of patients presented with ADRs were almost similar when compared to patients without ADRs [male 45.25% against 42.94% male). Number of medications prescribed was same in both ADR and non ADR group (median 2, range: 1 to

13 drugs). Majority of the patients were diagnosed to have had a depression in both ADR and non ADR groups [(n = 98) 57.64%, against (n = 123) 53.24%].

Of the 208 suspected ADRs identified, four ADRs could not be evaluated for causal relationship due to the non-availability of the data. Of the 204 ADRs, 71.07% (n = 145) of the ADRs were detected by intensive monitoring while 28.92% (n = 59) of ADRs were spontaneously reported. Forty-five kinds of ADRs were observed in the study patients. Gastrointestinal system [(n = 54) 26.47%] was the most commonly affected system organ class. Among all ADRs reported, dry mouth (n = 30) was the most commonly observed ADR followed by diaphoresis (n = 21). [Table 1] shows the system organ class affected by ADRs. Selective serotonin reuptake inhibitors (SSRIs) [(n = 110) 53.92%] were the most common class of antidepressants implicated in the reported ADRs. The class of antidepressants most commonly implicated in ADRs is shown in [Table 2].{Table 1}{Table 2}

As assessed by the WHO probability scale, 125 (61.27%) ADRs were 'probable' in their causality category. Majority of [n = 184 (90.17%)] ADRs were 'mild' in their severity and in 33 cases of suspected drug was restrained. Predictable reactions accounted for 166 (81.37%) whereas 158 (77.45%) ADRs were not preventable. The details of the assessment of ADRs are given in [Table 3].{Table 3}


This prospective study finding highlights the incidence and pattern of ADR to antidepressants in Indian psychiatric patients. The prevalence of ADRs to antidepressants in our study was 42.4%, which was higher when compared to an Indian study (26.87%) conducted by Swati et al. [13] and a western study (1.87%) conducted by Grohmann et al. [6] This difference could be because of the differences in the methodology adopted. Our study included both inpatients as well as outpatients and while Swati et al. [13] study included only outpatients. The difference in incidence between this study and Grohmann et al. [6] study could be due to the reason that our study focused on all ADRs, while Grohmann et al. [6] study focused only on new and severe ADRs.

Present study adopted both active surveillance and spontaneous reporting of ADRs. Majority of the ADRs were reported by active surveillance. However, it was observed that spontaneous reporting rate was increased after the presence of clinical pharmacist in the psychiatric outpatient department (OPD). This finding suggests that pharmacist's involvement in the OPDs increased the spontaneous reporting of ADRs.

The most common organ system affected by ADR was gastrointestinal system (26.7%). This finding is in contrast to the study conducted by Swathi et al., [13] wherein cardiovascular system was the predominant system affected by the ADR. Dry mouth and diaphoresis were the most commonly reported ADRs. This may be attributed to the possible pharmacological actions of the drugs implicated in causing ADRs. This finding is in contrast to the study conducted by Swathi et al., [13] wherein insomnia was the most commonly reported ADR. This difference could be due to the reasons that in our study, SSRI were the most commonly prescribed class of drugs. SSRIs have minimal effects on histamine H1 receptors and therefore can cause less sleep disturbances than other antidepressants. We also observed 10 cases of weight gain over a period of 10 weeks. It is well known that antidepressants like mirtazapine can increase appetite and carbohydrate craving and that may lead to significant weight gain. [10]

Majority of the ADRs were due to SSRIs and SNRI. This could be attributed to increased frequency of used prescription of these drugs due to lesser ADRs. Escitalopram was widely prescribed and was the most common drug implicated in causing ADR. Fatigability was most commonly associated with the patients who were on SSRIs. Anorexia and excessive yawning were the most commonly reported adverse reactions to desvenlafaxine and they occur early in the treatment. This study observed 13 cases of orthostatic dizziness due to TCA (n = 8) and desvenlafaxine (n = 5) and these subsided within the first few days to weeks of the therapy. Since SSRI do not block alpha-1 adrenergic receptors significantly, orthostatic hypotension is unlikely in patients receiving SSRIs. [14]

When assessed by using the WHO probability scale, none of the ADRs belonged to 'certain' in their causality category, no case had as rechallenge was not attempted in all those cases were there was dechallenge. This finding can immensely be correlated with the most of the Indian studies [5],[13] but in contrast to Brazilian study [9] wherein 24 cases were categorized as 'definite' in their causality category after the positive rechallenge. Most of the reported ADRs were 'mild' to 'moderate' in their severity and hence did not require withdrawal of the suspected drug when the benefits outweighed the risk. None of the reported ADRs in our study was fatal. However, a case of mania was reported with clomipramine necessitating hospitalization for a week.


The incidence of adverse reaction due to antidepressants was 42.3%, with SSRI being the most common class of drugs implicated for the ADRs. This prospective surveillance study provides a representative data of ADR profile of the antidepressants likely to be encountered in Indian psychiatric patients. Constant vigil in early detection and reporting of ADRs and subsequent management can make the therapy with antidepressants safer and effective.


We thank JSS University and Principal, JSS College of Pharmacy, Mysore. We also thank all the staff in mental health department of JSS Hospital, Mysore for their support and encouragement.


1Depression: A global crisis world mental health day, October 10. 2012. Available from: [Last accessed on 2012 Oct 10].
2American Psychiatric Association. Practice guidelines for the treatment of patients with major depression disorder (Revision). Am J Psychiatry 2000;157:1-45.
3Lin EH, Von Korff M, Katon W, Bush T, Simon GE, Walker E, et al. The role of the primary care physician in patients' adherence to antidepressant therapy. Med Care 1995;33:67-74.
4Zajecka JM. Clinical issues in long term treatment with antidepressants. J Clin Psychiatry 2000;61:20-5.
5Sengupta G, Bhowmick S, Hazra A, Datta A, Rahaman M. Adverse drug reaction monitoring in psychiatry out-patient department of an Indian teaching hospital. Indian J Pharmacol 2011;43:36-9.
6Grohmann R, Hippius H, Helmchen H, Rüther E, Schmidt LG. The AMUP study for drug surveillance in psychiatry - a summary of inpatient data. Pharmacopsychiatry 2004;37:s16-26.
7Shah LP, Ayyar KS, Agarawal BR, Pradhan PV, Bagadia VN, Gupta KC, et al. Drug surveillance programme in psychiatry- adverse drug reactions. Indian J Psychiatry 1983;25:229-34.
8Zabo CP. Common adverse drug reactions with psychiatric medications and an approach to their management. CME 2011;29:230-2.
9Carlini EL, Nappo SA. The pharmacovigilance of psychoactive agents in Brazil. Rev Bras Psiquiatr 2003;25:200-5.
10Khawam EA, Laurencic G, Malone DA Jr. Side effects of antidepressants: An overview. Cleve Clin J Med 2006;73:351-3, 356-61.
11Richelson E. Pharmacology of antidepressants. Mayo Clin Proc 2001;76:511-27.
12Richelson E. Interaction of antidepressants with neurotransmitter transporters and receptors and their clinical relevance. J Clin Psychiatry 2003;64:5-12.
13Mishra 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. Available from: - 4985 [Last accessed on 2014 Jan 28].
14Masand PS, Gupta S. Long-term side effects of newer-generation antidepressants: SSRIs, venlafaxine, nefazodone, bupropion, and mirtazapine. Ann Clin Psychiatry 2002;14:175-82.