A Drug Use Evaluation Study on Antidepressants in Psychiatric Patients at a Tertiary Care Teaching Hospital

Background: The pattern of prescribing Antidepressants to patients has been varying worldwide. Objective: We aim to observe the prescribing pattern of antidepressants as well as assess its various outcomes in patients, the rationality of the prescriptions, and the prevalence of antidepressant usage. Methodology: A prospective observational study of a total of 56 subjects receiving antidepressants was performed at the Psychiatry. They were screened for their various outcomes on using antidepressants. The written form of the medical record sheet was used to preserve the patient's Data. Prescription pattern, treatment chart, abnormal vitals were noted. Morisky's adherence scale was used to assess the adherence of patients to prescribed drugs. Hamilton depression rating scale was used to measure the patient's depressive stage. They were screened for possible ADRs. Original Research Article Hadia et al.; JPRI, 33(40A): 66-75, 2021; Article no.JPRI.71980 67 The causality and severity assessment of the observed ADRs was done by the WHO-UMC scale and Hartwig-Seigel scale respectively. Statistical analysis was done for all relevant data. Results: In our study, the age of patients varies from 18 years to 85 years. The maximum number of patients were from the age group of 31-40 years [28.57% (N=16)]. The 50% (N=28) of patients were diagnosed with Depressive mood disorder. A total of 169 drugs were prescribed out of which 52.07% (N=88) were Antidepressant drugs. Out of 88 Antidepressant drugs, 20% (N=18) patients received Venlafaxine, followed by 17% (N=15) Escitalopram. Out of 56, 26.78% (N=15) showed low adherence, 41.07% (N=23) showed medium adherence and 32.14% (N=18) showed High adherence.41.07% (N=23) patients were identified with drug use problems. Adverse drug reactions were suspected in 25% (N=14) patients. The most common type of Adverse reaction due to the drug was Weight gain (N=6 patients). Paroxetine drug was found with the highest number of ADRs 28.57% (N=4). Conclusion: Most common antidepressant prescribed was Venlafaxine. Most Patients in the community included suffered from Depressive mood disorder with a maximum number of patients appeared from the age group of the thirties to forties. Patients due to their unstable mental status were adhering to therapy at medium levels. Drug use problem was identified commonly with patients on sedatives resulting them to either forget taking the pills or missing the dose. Patients generally had a common Adverse drug reaction of weight gain. Proper lifestyle modifications and patient counselling is required to benefit patient from treatment.


INTRODUCTION
The prevalence rate in the Indian population of psychotic disorders ranges from about 9.5-370/1000 populations [1]. Drug use evaluation (DUE) plays an important role in rationalizing the therapy. Rational drug prescribing is the process in which polypharmacy is avoided by using proper drugs which give the required therapeutic effect along with minimum possible side effects in the least time and also at an affordable price for patients [2]. The only purpose of DUE is to make sure that the drugs are utilized effectively with their correct and safe usage in the best patient healthcare. Every pharmacist plays an important role in the establishment of the DUE program. DUE is performed to inspect the aspects which are directly associated with medication use. DUE data helps in improving prescribing formulary compliance and patient compliance [3]. It is an essential component of medical audit and hence allows pharmacists to monitor and analyze the prescribing patterns of medicines, to make appropriate modifications in the prescribing patterns for rational therapeutic practice and also cost-effective patient care and also as a tool to study the clinical use of drugs in populations and its influence on our health-care system [4,5]. DUE aims to evaluate the rationality of therapy and to reach the goals, auditing methods for drug therapy regarding rationality. DUE may evaluate drug used at a population level, according to sex, age, morbidity, social class, among other characteristics [6]. DUE also increases our understanding of how drugs are being used [7]. It also provides perception into the productivity of drug usage, i.e., whether a particular drug therapy gives value for money and the results of the research are used to help to set priorities for the rational administration of health care budgets [8]. We aim to observe the prescribing pattern of antidepressants as well as assess its various outcomes in patients, the rationality of the prescriptions, and the prevalence of antidepressant usage.

METHODOLOGY
It was a prospective observational study conducted for 6 months at the Department of Psychiatry, Dhiraj General Hospital, Vadodara. All patients between age 18 years to 85 years attending the department of psychiatry and diagnosed with any clinical condition as per DSM-5 criteria in which antidepressant drugs were prescribed were included in a study after explaining to the patients, the details of the study. The patient's medical records were checked and the following information was noted in the Patient Medical Record sheet: Patient's demographic details, Patient Medical History, Diagnosis and duration, family history, presence of other co-morbidities, Prescribed drugs including Antidepressants (Frequency, Dose, Route of administration and Duration) was also collected, Drug interaction, Cost of drugs, Lab investigations reports (which are already mentioned inpatient medical records). All the relevant data was obtained from the patients' medical records and through counseling the patients who visited the Out-Patient Department (OPD) or In-Patient Department (IPD). Morisky's adherence scale was used to assess the adherence of patients to prescribed drugs. Hamilton depression rating scale was used to measure the patient's depressive stage. They were screened for possible ADRs. The causality and severity assessment of the observed ADRs was done by the WHO-UMC scale and Hartwig-Seigel scale respectively. All the relevant data collected and recorded electronically. Descriptive statistics used for the analysis of the data. After the data collection, all the data were exported to statistical software for statistical analysis. All the quantitative data were represented in mean ± standard deviation. Comparative statistical differences were calculated using appropriate parametric tests.

RESULTS
A total of 56 patients were included in the study. They were diagnosed with different types of Psychiatric illnesses like Depressive mood disorder, Anxiety, Panic disorder, Bipolar mood disorder-1, Major depressive mood disorder, etc., and were further screened for various outcomes of antidepressants. Out of 56 patients, 25% (N=14) patients were affected by ADRs irrespective of their severity. Comparing the gender proportionality, male represents 64.29% (N=36) while female represents 35.71% (N=20). In our study, the age of patients varies from 18 years to 85 years with a mean age of 51 years. The maximum number of patients were from the age group of 31-40 years [28.57% (N=16)] followed by age group 41-50 years [23.21% (N=13)], and lastly, the least number of patients [1.78% (N=1)] were found in the age group of >70 years.
In our study, we noted that the maximum number of patients were diagnosed with Depressive mood disorder comprising 50% (N=28), followed by Major Depressive mood disorder with anxiety 16.07% (N=9), Major depressive disorder with 12.50% (N=7), Bipolar mood disorder-1 with 7.14% (N=4), and Anxiety with 3.57% (N=2 According to the suspected diagnosis, medications were prescribed which contained Antidepressants along with other classes of medications. Of 56 OPD patients, a total number of drugs prescribed were 169 out of which 52.07% (N=88) were Antidepressant drugs and the remaining 47.92% (N=81) were drugs of class other than an antidepressant. Out of 56 patients included, 51.79% (N=29) of patients received 1 antidepressant drug in their prescription followed by 37.50% (N=21) of patients who received 2 antidepressant drugs, other data is mentioned in Table 4. Out of 56 patients prescribed with 88 Antidepressant drugs of various class, 20% (N=18) patients received Venlafaxine, followed by Escitalopram with 17% (N=15), Fluoxetine with 14% (N=12), Sertraline 13% (N=11), and other drugs of different antidepressant class are mentioned in Table 5. Out of 56 patients prescribed with 81 non-Antidepressant drugs of various class, 37.04% (N=30) patients received Clonazepam, followed by Olanzapine with 18.52% (N=15), Multivitamin with 9.88% (N=8), Lithium and Trifluoperazine with 6.17% (N=5), and other drugs of different non-antidepressant class are mentioned in Table  6. Drug use problems: For a psychiatric patient with altered mental status or imbalance in brain functions, using drugs prescribed might be a challenging thing. Drug using problems play an important role in treating a patient. In our study out of 56 patients, 41.07% (N=23) patients were identified. Cases of Drug dosing problem were identified with category a (wrong drug dose) where the patient took the wrong drug dose. 21 patients were categorized under Drug usage problem with category (Drug not taken at all, Wrong drug taken, Drug used without indication respectively).

DISCUSSION
A total of 56 patients were included in the study according to the inclusion and exclusion criteria. Out of 56 patients, 25 % (N=14) patients were affected by ADRs. Out of 56 outpatients selected for the study Comparing the gender proportionality, male represents 64.29% (N=36) while female represents 35.71% (N=20) of the population. In our study, the age of patients varies from 18 years to 85 years with a mean age of 51 years. The maximum number of patients were from the age group of 31-40 years [28.57% (N=16)] followed by age group 41-50 years [23.21% (N=13)], and lastly, the least number of patients [1.78% (N=1)] were found in the age group of >70 years in contrast to S. CHAKRABARTI et al. [9] with Majority of the sample were females (58%), half of them aged between 20-39 years, and a little more than a quarter (26%) in the age range of 40-49 years. According to the suspected diagnosis, medications were prescribed which contained Antidepressants along with other classes of medications. Of 56 OPD patients, a total number of drugs prescribed were 169 out of which 52.07% (N=88) were Antidepressant drugs and the remaining 47.92% (N=81) were drugs of class other than an antidepressant. Out of 56 patients included, 51.79% (N=29) of patients received 1 antidepressant drugs in their prescription followed by 37.50% (N=21) of patients who received 2 antidepressant drugs, in contrast, to a study conducted by S. CHAKRABARTI et al. [9] where 64% (N=69) patients received 1 antidepressant drug and 18%(N=19) patients received 2 antidepressant    [10] wherein Antidepressants were prescribed in 76.18% prescriptions (duloxetine -50%, escitalopram -22.40%, mirtazapine-17.19%, sertraline-6.77%, and others-3.64%). Drug-drug interactions are most common amongst Psychiatric patients. In our study, Drug-drug interactions were identified using a software database (E.g., Medscape and Micromedex interaction checker). Further, this interaction was identified in patients by a verbal discussion with patients noting the description of the event experienced. Out of 56 patients, Prescribed Antidepressants and Non-antidepressant drugs, 60.71% (N=34) patients did not experience any drug-drug interactions, however, 39.28% (N=28) patients experienced the interactions.
Based on the complaints and experiences of patients on consuming the drugs, out of 56 patients selected for the study, ADR was suspected in 25% (N=14) patients. The remaining 75% (N=42) did not experience ADR. Out of 14 patients suspected of ADR, the most common type of Adverse reaction due to the drug was Weight gain (N=6 patients), followed by Tremors (N=2 patients), itching with burning sensation (N=2), Muscle weakness (N=1), and blackening of skin (N=1), Jerky hand movements (N=1) and Weight loss (N=1). Of 14 people experiencing ADRs Paroxetine drug was found with the highest number of ADRs 28.57% (N=4) followed by Venlafaxine with 21.42% (N=3), Mirtazipine14.28% (N=2), and other drugs like Divalproex, Olanzapine, Fluoxetine, Risperidone, and Lorazepam with 7.14% (N=1) Higher than the result found in the study carried out by Munoli S., et al. [11] (5.2%), lower than that of the study conducted by Lucca JM., et al. [12] (34.24%) and Shah L., et al. [13] (32.8%). Causality Assessment by WHO-UMC Causality Assessment was performed by WHO-UMC Scale, out of 14 ADRs majority of ADRs was found to be Possible with 50% (N=7) followed by Probable with 28.57% (N=4) and Unclassifiable with 21.42% (N=3). in contrast to a study carried out by Shah A. et.al. in which maximum ADRs were classified 'probable' followed by 'possible'. No 'certain' causes were seen since in cases where DE-challenge was done, rechallenge was not attempted with the offending drug. This is following to study carried out by Munoli S.et al. [11] For 56 patients included in the study, the Morisky medication adherence scale was used to assess adherence. Based on their oral viva individual score was calculated. Patients who scored ≥8 points, <8 to >6 points and ≤ 6 points on the scale were considered to have High, Medium, and Low Adherence respectively. Out of 56, 26.78% (N=15) showed low adherence, 41.07% (N=23) showed medium adherence and 32.14% (N=18) showed High adherence, then study performed by Shrestha mandhar et al. [14] wherein Less number (37%) of the patients were adherent to the antidepressant therapy.

CONCLUSION
Our study shows that depressive mood disorder was the most common psychiatric diagnosis in the population and that out of antidepressants Most common antidepressant prescribed was Venlafaxine, followed by Escitalopram, Fluoxetine. Most Patients in the community included suffered from Depressive mood disorder with a maximum number of patients appeared from the age group 31-40 years. The preference for Venlafaxine over SSRIs as the first-line drug in depressive disorders did not conform to the standard prescribing guidelines. Most of the patients were treated with a single antidepressant. However, poor response and/or tolerability considerations made the prescribers change the antidepressant or add a second antidepressant. Antidepressants were prescribed for many indications other than depressive disorders and the psychiatrists' choice of the drug was influenced by the diagnosis, the severity of the disease/disorder, co-morbidity, drug efficacy, and the considerations for the patients' tolerability. The prescriptions were complete and polypharmacy was not seen. The consumption of antidepressants in the community was low. Adequate dosing was seen for all the antidepressants. Patients due to their unstable mental status were in majority of medium adherence levels (41.07%). Drug use problem was identified commonly with patients on sedatives resulting them to either forget taking the pills or missing the dose. Patients generally had a common ADR of weight gain. Proper lifestyle modifications and patient counseling is required to guide patient with mental instability and benefit them from treatment.