Drug utilization study and adverse drug monitoring of antidepressant drugs in a tertiary care hospital of Bihar

Background: Depressive disorders are amongst the most prevailing causes of morbidity and disability in the Indian population. Choosing suitable antidepressants for a particular patient is an imperative decision. Aim: To study the drug utilization of antidepressantdrugs and their adverse drug reaction in the department of psychiatry of a tertiary care hospital. Materials and Methods : It was an observational, prospective study conducted for a duration of 18 months, i.e., from February 2018 to July 2019. The ﬁrst six months were for recruitment of patients and 12 months were for follow up and data compilation. The prescriptions of every alternate patient were collected on a twice-weekly basis. Results: In our study, 21–30 years of age group accounted for majority (31.98%) of all depressive disorders . Males (52.28%) were found to be more affected than females. SSRIs (73.26%) were most frequently prescribed, followed by TCA (20%) and SNRI (6.33%). The average number of drugs per prescription was 2.49. The most commonly reported ADR was insomnia (21.23%). ADRs were more commonly found with nortriptyline; a tricyclic antidepressant drug. PDD/DDD values of most of the drugs were close to one. Conclusions: Through this study, we found that SSRIs were the most commonly prescribed group of antidepressants because of their better efﬁcacy, safety, tolerability, and fewer side effects as compared to TCAs. PDD/DDD ratio signiﬁes that the drugs were neither under-utilized nor over-utilized. Since no prescription had more than ﬁve drugs; we can say that polypharmacy was avoided. the the


Introduction
Depressive disorders are amongst the most prevailing causes of morbidity and disability in the Indian population. They are generally accompanied by negative thinking, sense of guilt or worthlessness, reduced interest to work, psychomotor anxiety, unhappy married life due to reduced libido, weight loss or gain because of altered eating patterns, etc. 1 They are also accompanied by other medical conditions such as chronic pain and ischemic heart disease. 2 Antidepressants are primarily used for the management of depressive disorders and many anxiety disorders. However, these are also used in the pharmacotherapy of a range of psychiatric disorders including obsessive-compulsive disorders, attention deficit hyperactivity disorder, eating disorders, personality disorder, impulse control disorders, enuresis, chronic pain, neuropathic pain, etc. irrespective of the existence of co-morbid depression in these situations. 3,4 Choosing suitable antidepressants for a particular patient depends on many factors like; patient's demographic profile, comorbidities, side-effects of the drugs, and costeffectiveness. In the last decade, there has been a gradual shift in the prescribing patterns of antidepressants from tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAO inhibitors) to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake https://doi.org/10.18231/j.pjms.2020.065 2249-8176/© 2020 Innovative Publication, All rights reserved. 315 Inhibitor (SNRIs). 5 The study of prescriptions can thus help in identifying the drug utilization pattern of these antidepressants. Drug utilization studies have been defined by the World Health Organization (WHO) as marketing, distribution, prescription, and use of drugs in a society, with consideration of its medical, social and economic consequences. 6 It has been estimated by WHO that depressive disorder will become the second most leading cause of morbidity and disability by the end of the year 2020. 7 In addition to this, the proliferation of new drugs, increasing recognition of delayed adverse effects and the increased focus in pharmacovigilance has stimulated interest in the study of prescription patterns. 8 Therefore, keeping these facts into consideration, we planned was to study the drug utilization of antidepressantdrugs and their adverse drug reaction in the department of psychiatry of a tertiary care hospital.

Materials and Methods
It was an observational, prospective study done on patients visiting the outpatient department (OPD) of Psychiatry in a tertiary health care centre. The study was conducted for a duration of 18 months, i.e., from February 2018 to July 2019. The first six months were for recruitment of patients and 12 months were for follow up and data compilation. The prescriptions of every alternate patient were collected on a twice-weekly basis. The study was commenced after getting approval from Institutional Ethics Committee.

Results
In our study, 21-30 years of age group accounted for the majority (31.98%) of all depressive disorders [ Table 1] In gender based analysis we found that males were more affected than females. [ Table 2] In our study, among antidepressants, SSRIs (73.26%) were most frequently prescribed, followed by TCA i.e. nortriptyline (20%) and SNRI i.e. venlafaxine (6.33%).
[ Table 3] The most commonly reported ADR was insomnia (21.23%) followed by dizziness (12.33%) and weight gain (10.96%). ADRs were more commonly found in nortriptyline; a tricyclic antidepressant drug. [ Table 4] In our study, PDD/DDD values of most of the drugs were close to one which signifies that drugs were not underutilized or over-utilized. [ Table 5] PDD/DDD value of sertraline, fluoxetine and nortriptyline was greater than 1. PDD/DDD values of most of the drugs were less than one and close to one.    11 In gender based analysis we found that males were more affected than females. 13,14 In our study, among antidepressants, SSRIs (73.26%) were most frequently prescribed, followed by TCA i.e. nortriptyline (20%) and SNRI i.e. venlafaxine (11.63%). Among SSRIs present drug utilisation was most in sertraline (23.06%) followed by fluoxetine (21.02%), escitalopram (11.63%), paroxetine (10%) and, fluvoxamine (7.55%). SSRI is the extensively prescribed antidepressants as they are generally free of sedative effects, safer at higher doses and have better tolerability with mild adverse effects. 15 In many other studies, including Tripathi et al. SSRIs accounted for majority of the prescribed antidepressants. [16][17][18][19] A total of 490 antidepressant drugs were prescribed in 197 prescriptions. The average number of drugs per prescription was 2.49. It is somehow in conformity with the study of Lahon et al. and Piparva et al who acclaimed 2.32 and 2.96 average number of drugs per prescriptions in their study. 10,20 Polypharmacy can lead to poor compliance, drug interactions, adverse drug reactions, and medication errors. 21,22 Since no prescription had more than five drugs, we can say that polypharmacy was avoided. In our study 146 ADRs were found in 197 patients. Most commonly reported ADR was insomnia (21.23%) followed by dizziness (12.33%) and weight gain (10.96%). ADRs were more commonly found in nortriptyline; a tricyclic antidepressant drug. 23,24 Defined Daily Dose (DDD) is the assumed average maintenance dose per day for a drug used for its indication in adults. 25 The prescribed daily dose (PDD) is the average dose, prescribed according to a representative sample of prescriptions. It is important to relate the PDD to the diagnosis on which the dosage is based. The PDD will give the average daily amount of a drug that is actually prescribed. PDD is especially important for drugs where the recommended dosage differs from one indication to another. When there is a substantial discrepancy between the PDD and DDD, it is imperative to take this into consideration when evaluating and interpreting drug utilization figures, particularly in terms of morbidity. 26 The ratio of PDD to DDD is often used as an indication of the adequacy of dosing. When this ratio is either less than or greater than one, it may indicate that there is either under or over utilization of drugs. Nevertheless, it is important to note that the PDD can vary as per patient and disease factors. In our study, PDD/DDD values of most of the drugs were close to one which signifies that drugs were not under-utilized or over-utilized.
The limitation of our study was that we did not study the appropriateness of prescribing antidepressant drugs with regard to diagnosis and comorbidities. We were not able to study certain factors, such as; patient compliance, patient care indicators, adherence to treatment guidelines, and cost, which can broaden the utility of a study. Further, in our study patients of depression with psychotic symptoms, elderly depressed patients, and patients in the child and adolescent age group were excluded. Future studies should try to overcome these limitations.

Conclusion
This study was a sincere attempt to see the drug utilization of antidepressants and their ADRs. We found that SSRIs were the most commonly prescribed group of antidepressants because of their better efficacy, safety, tolerability, and fewer side effects as compared to TCAs. Among SSRIs sertraline was most frequently prescribed. The average number of drugs per prescription was 2.49. Since no prescription had more than five drugs; we can say that polypharmacy was avoided. ADRs were more frequently found in nortriptyline; a tricyclic antidepressant group.

Acknowledgement
We are thankful to the doctors of psychiatry department of IGIMS, Patna for their support.

Sources of Funding
Nil.

Conflicting Interest
Nil.