INTRODUCTION:

Depressive disorders have a substantial impact on global health. According to a Global Health Estimate the prevalence of such mental health disorders is more than 300 million, being the fourth leading cause of disability and premature death¹.

They constitute an estimated 7.4% of the world’s measurable burden of disease². Major Depressive Disorder (MDD) being the second leading cause of years lived with disability (YLDs) globally is the four largest contributor to YLDs in socially diverse regions across the six continents². In India, the prevalence of depressive disorders was 50 million or 4.5% of population in 2015 and total Years Lived with Disability (YLD) was over 10 million years (7.1%).³^,⁴^,⁵

As a class of drugs, antidepressants are used primarily in the management of depressive and anxiety disorders. The drugs used in the management of depression include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitor (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors and atypical antidepressants that primarily effect on the serotonergic or the noradrenergic neurotransmitter system.⁶^,^7,⁸^,9

Occurrence of adverse drug reactions (ADRs) lead to noncompliance and discontinuation of the therapy.¹⁰^,¹¹^,^12,^13,¹⁴^,15 Updated information on the ADRs of these drugs and the knowledge of risk benefit balance is likely to influence the compliance to treatment.

As there is little data available in terms of safety of antidepressants in the local population, this study was done to analyze the ADR profile of antidepressant drugs in a mental health institute in Odisha.

MATERIAL AND METHODS:

Study Design:

This is a hospital based cross-sectional, observational, descriptive study.

Study Setting:

The study was conducted in Department of Pharmacology in collaboration with Mental Health Institute(Centre of Excellence), SCB Medical College and Hospital, Cuttack.

A study team was constituted comprising of principal investigator and co authors. The study protocol was designed by the team.

Study Period:

The research work was carried over a period of two years from September 2017 to September 2019.

Study Population:

All patients receiving antidepressants, both as outpatient or inpatient, in the Department of Psychiatry, SCB Medical College and Hospital, Cuttack.

Sample Size:

Sample size was calculated to be 180 using the formula

Sample size (n) = [{Z_1-α/2}² p(1-p)] _/d²¹⁶

Where ‘p’ is prevalence of antidepressant use and‘d’ is allowable error.

Ethical Permission:

The study was approved by institutional ethics committee.

Study Subjects:

This study was conducted on patients receiving antidepressants in Department of Psychiatry fulfilling the following criteria:

Inclusion criteria-

All subjects receiving antidepressant medication attending the department of Psychiatry and willing to participate.

Patients of all age groups and both sexes.

Study Procedure:

Demographic details of selected subjects like age, sex, educational, marital and employment status noted in prestructured case record form (CRF). Clinical details like diagnosis, antidepressant used, dosage, route of administration, frequency and duration of treatment noted in CRF. Subject were questioned and assessed for any occurrence of adverse drug reaction (ADR). If ADR present, details of it was noted on suspected ADR reporting form given by PvPI. Causality, severity and preventability of ADRs were assessed by, WHO-UMC causality assessment¹⁷, modified Hartwig-Siegel Scale¹⁸ and modified Schumock-Thornton criteria respectively.¹⁹

Statistical Analysis:

Results were analyzed using descriptive statistics like mean ± SD, percentages and proportions. Significance, when required, was tested using chi square test at two sided α level at 5%. All the analysis was done by using Microsoft Excel and SPSS v.20.

RESULTS:.

Our study had a total of 180 patients enrolled. Of them majority were females, i.e, 99 (55%) compared to males, i.e, 81(45%). The mean age of the study subjects was 47.5 ± 6.7 years. Most of the subjects, i.e, 70 (38.9%) belonged to the age group of 36-50 years, followed by 51-64 years age group with 55 (30.5%).

Depressive disorders were the primary reason for taking antidepressants (42%) followed by anxiety disorders with 28%.[Fig.-1]

Figure 1: Types of diseases observed

A total of 43 patients were found to have adverse drug reactions. Some of them had more than one adverse event. A total of 52 adverse events were noted. Insomnia with 14(27%) cases was most common adverse effect. This was followed by fatigue and agitation or nervousness with 9(17.3%) and 7(13.5%) cases respectively. [Table 1]

Table 1: Adverse drug reaction profile (N=52)

ADRs	Frequency (n)	Percentage (%)
Insomnia	14	26.9
Fatigue	9	17.3
Agitation/ Nervousness	7	13.5
Sexual Dysfunction	4	7.7
Increased Sweating	4	7.7
Headache	4	7.7
Nausea	3	5.8
Dry Mouth	3	5.8
Loss of Appetite	2	3.8
Tachycardia	2	3.8
Total	52	100

In our study 24.7% males showed adverse drug reactions in comparison to 23.2% of all females. This difference in incidence was not significant statistically. (Chi Square Test, p=0.84)

Table 2: Distribution of ADRs by gender (N=180)

Gender		ADR		Total
Gender		Present	Absent	Total
Male	Count	20	61	81
	% Within Gender	24.7	75.3	100
	% of Total	11.1	33.9	45
Female	Count	23	76	99
	% Within Gender	23.2	76.8	100
	% of Total	12.8	42.2	55
Total	Count	43	137	180
Total	% of Total	23.9	76.1	100

Most number of the patients with ADRs belonged to the 6 to 9 months of antidepressant therapy group with 23 cases. The incidence of ADRs increased with increase in duration of therapy with highest seen in more than 9 months of treatment (44%). [Fig-2]

Figure 2: ADRs in relation to duration of therapy

The incidence of ADRs was higher in polytherapy group (34.4%) compared to monotherapy (21.6%). This was not a statistically significant difference. (Chi Square Test, p=0.18) [Table 3]

Table 3: ADR in Relation to Type of Therapy (N=180)

Type of Therapy		ADR		Total
Type of Therapy		Present	Absent	Total
Monotherapy	Count	32	116	148
Monotherapy	% In Type of Therapy	21.6	78.4	100
Polytherapy	Count	11	21	32
Polytherapy	% In Type of Therapy	34.4	65.6	100
Total	Count	43	137	180
Total	% of Total	23.9	76.1	100

In our study most number of patients with ADRs, i.e, 15 cases were receiving only SSRIs. This was followed by patients with polytherapy (SSRI plus some other drug) with 11 cases and SNRIs only group with 10 cases. But incidence wise TCAs were most unsafe with 50% of patients showing ADRs followed by polytherapy with 34.4% patients showing ADRs. TCAs showed statistically significant higher incidence of ADRs compared to SSRIs (p= 0.04) and SNRIs (p= 0.03). (Chi Square Test) [Fig 3]

Figure 3: ADRs in relation to group of antidepressant drugs

According to WHO – UMC causality assessment system, 25 patients with ADR were assessed to be grouped in ‘Possible’ category and 18 patients were assessed to be in ‘Probable’ category. None of the 43 patients with adverse reactions belonged to any of the other categories. Most of the ADRs, i.e., 39 (90.7%) were ‘Mild’ and 4 (9.3%) were ‘Moderate’ based on Hartwig Siegel Scale. None of the study subjects showed any severe adverse drug reaction. Based on modified Schumock – Thornton criteria, 36 (83.7%) patients had ADRs which were ‘Not Preventable’ and 7 (16.3%) had ADRs which were ‘Probably Preventable’. None of the patient had any ‘Definitely Preventable’ adverse drug reaction.

Table 4: Causality assessment of ADRs (N=43)

WHO-UMC Category	Frequency (n)	Percentage (%)
Certain	Nil	Nil
Probable	18	41.9
Possible	25	58.1
Unlikely	Nil	Nil
Conditional	Nil	Nil
Unclassifiable	Nil	Nil
Total	43	100

Figure 4: Severity assessment of ADRs

Figure 5: Preventability assessment of ADRs

DISCUSSION:

We have conducted this study with an aim to assess the incidence and profile of suspected ADRs associated with antidepressant medications in a mental health institute in Odisha. Demographic analysis did not confer any significant higher incidence of adverse drug reactions to female compared to males (p = 0.18), a congruent finding to Mishra et al and Mukherjee et al.²⁰^,²¹

Analysis of the diagnostic pattern suggested that depressive disorders were the most common psychiatric illness encountered followed by anxiety disorders. This finding is similar to Mukherjee et al and Sridhar et al.²¹^,²²

In our study incidence of ADRs was about 24% with insomnia (8%), fatigue (5%) and nervousness/agitation (4%) being the most common among them. These findings are somewhat similar to that by Mishra et al where insomnia and agitation were top most ADRs²⁰ and Mamatha et al where insomnia was most common.²³

In our study the incidence rate of ADRs gradually higher with the increase in duration of therapy, with highest incidence (44%) in more than 9 months of treatment group. This difference in incidence rate of ADRs between groups was statistically significant, clearly suggesting that with increased duration of therapy there is definitely increase in development of adverse drug reactions,

The incidence of ADRs was higher in patients who received more than one antidepressants compared to those who received just one. This difference however wasn’t significant statistically. With a higher sample size may be a significant difference can be elucidated.

Most numbers of ADRs were seen in patients receiving SSRIs, a finding similar to almost all published studies. This could be due to the higher rate of usage of SSRIs compared to other groups. When classes of antidepressants were compared with each other TCAs had higher incidence of ADRs compared to SSRIs and SNRIs, which was statistically significant. This again is a similar finding to almost all the published studies. There was no statistically significant difference in ADR incidence rate of SSRIs compared to SNRIs. This is similar to findings by Mukherjee et al, Sharma et al and Shah et al.²¹^,24^,²⁵

In causality assessment by WHO-UMC system 52% ADRs were ‘Possible’ and 48% were ‘Probable’ in our study. None of the ADRs were assessed to be ‘Definite’ as no discontinuation or rechallenge was done. These results are in congruence to findings by Mukherjee et al and Mishra et al. (21)(20)Lucca et al found a higher incidence of Probable (61%) ADRs compared to Possible (39%).²⁶

Severity assessment of ADRs done by using modified Hartwig – Siegel scale found that in our study majority (91%) of ADRs were of ‘Minor’ severity and few (9%) of ‘Moderate’ severity. There was no hospitalization or any permanent damage or any fatality due to the ADRs. So none of the ADRs can be classified as ‘Severe’. This finding is similar to that of findings of Mishra et al, Mukherjee et al, Lucca et al and Sengupta et al.²⁰^,²¹^,26^,27

In our study none of the ADRs were ‘definitely preventable’ while a very few (16%) were ‘probably preventable’. Most of the ADRs were ‘not preventable’ indicating towards the inevitable nature of ADRs with treatment by antidepressants. These findings are similar to the findings by Lucca et al, Mukherjee et al, Sharma et al and Shah et al.²¹^,²⁴^,²⁵^,²⁶ One study by Thomas et al found the rate of definitely preventable ADRs to be at 20%.²⁸ The lower rate of preventable ADRs might indicate towards proper diligence by the treating psychiatrists at our centre in prescribing suitable antidepressant based on patient’s clinical profile.

The current study focuses mostly on the prevalence of ADRs and their nature among antidepressant users, but is limited by its cross sectional nature and single setup. Multicentric prospective studies will bring about even better understanding about ADRs in this specific population.

CONCLUSION:

A moderate incidence of ADRs in patients receiving antidepressant drugs was found in the current study among which insomnia was the most common. SSRIs were the most common group to have ADRs but TCAs were most unsafe. Nature of majority of the ADRs reported in the study was mild and they were of not preventable type. But with better scrutiny the probably preventable adverse drug reactions can be avoided paving way for better use of antidepressants.

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Received on 30.11.2020 Modified on 01.01.2021

Research J. Pharm.and Tech 2021; 14(12):6479-6483.

DOI: 10.52711/0974-360X.2021.01120