Psychotropic Drugs Used in Psychiatry Outpatient Department: A Cross-Sectional Drug Utilization Research

: Mental and behavioral disorders are common around the world. Pharmacotherapy, psychotherapy, and psychosocial rehabilitation are three treatment components for these disorders. Drug therapy is an essential part of the comprehensive treatment of these diseases. Their use pattern in psychiatric practice has changed dramatically in recent years. Mental disorders require long-term treatment. Therefore, it is crucial to study the prescribing practices of these groups of drugs. This study aims to assess drug use patterns using the WHO/INRUD Core Prescribing Indicators. Patients of both genders and ages with mental illness and prescription psychiatric drugs were evaluated from the outpatient department of the Psychiatry Unit (OPD). The prescription data were collected and analyzed using the indicators recommended by the WHO/INRUD. The data were analyzed using Microsoft Excel-2007. The percentage and average values of the variables were compared. A total of 655 prescriptions were analyzed. Male patients (54.96%) were more than women (45.04%). The morbidity profile included schizophrenia (37.86%), alcohol use disorder (18.78%), major depressive disorder (11.30%), anxiety disorder (10.23%), bipolar disorder (4.88%), and others (16.95%). The newer antipsychotic were the most commonly prescribed drugs (particularly olanzapine), along with a central anticholinergic (trihexyphenidyl) and a benzodiazepine (lorazepam). The percentage of drugs prescribed with generic names was 39.80%, and that of drugs prescribed by NLEM was 48.49%. The average number of drugs prescribed per prescription was 2.58. This study's Index of Rational Prescribing (IRDP) was 3.87, whereas the optimal score was 5. Prescriptions were complete, and principles of rational prescribing were followed, except for a low generic prescribing rate.


Introduction
Drug utilization research (DUR) is defined by the World Health Organization (WHO,1977) as "the marketing, distribution, prescription, and use of drugs in society, with particular emphasis on the medical, social, and economic consequences". The main goal of drug use research is to facilitate the rational use of drugs in the population. For an individual patient, reasonable drug use means prescribing a well-studied medication at an optimal dose, with correct information, and at an affordable price (1). DUR is important in pharmacoepidemiology due to its close association with-public health, pharmacovigilance, pharmacoeconomics, and pharmacogenetics (2).
Mental disorders are included in the Global Burden of Diseases (3). Epidemiological studies in India indicate an incidence rate of around 18-20 per thousand of the population. Pharmacological therapy, psychotherapy, and psychosocial rehabilitation are the main components of treating mental illness (4). The prescription pattern of psychotropic medication use in psychiatric practice has changed dramatically (5).

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Saikia H (2023) -10.58920/sciphar02030042 https://etflin.com/sciphar 43 Many new psychotropic drugs are available to treat mental disorders and have radically changed the therapeutic protocols (6). The rapidly evolving field of psychopharmacology challenges traditional concepts of psychiatric treatment and constantly seeks new and improved drugs to treat these disorders. At the same time, the drugs should also be safer and efficacious (7).
According to the Global Burden of Disease Study 1990-2017 across the states of India, mental disorders included depressive disorders, anxiety disorders, schizophrenia, bipolar disorder, idiopathic development, intellectual disability, conduct disorder, autism spectrum disorders, eating disorders, attention-deficit hyperactivity disorder (ADHD), and other mental disorders (8). Among these, schizophrenia is one of the most common and burdensome psychiatric disorders in adults worldwide (9). Some previous DUR indicates that schizophrenia (6,7,10) and depression (11,12) were commonly encountered psychiatric disorders in India.
Irrational prescribing is a global problem. Prescribing errors promote irrational use of drugs, decrease patient compliance, and increase the cost and duration of the treatment. Such practices also lead to the emergence of drug interactions, drug resistance, and adverse drug reactions, which increases the rate of mortality and morbidity (13). Psychotropic medications prescribed to manage psychiatric disorders usually follow the guidelines formulated by various organizations. However, it is often discussed that many patients receive irrational prescriptions, which either do not provide any benefit to the patients or harm them (14).
Psychiatric illnesses are chronic and may profoundly impact the sufferer's quality of life, family members, and society (15). The problem may compound with inappropriate and irrational prescribing.
In the form of DUR, periodic prescription audits can improve rational prescribing and prescription quality. Keeping in view the principle aim of DUR to facilitate the rational use of drugs in the population, this study was undertaken to investigate the prescription pattern of psychotropic drugs and also to assess the rationality of the prescriptions in an outpatient department of psychiatry unit in a tertiary care teaching hospital in Assam.

Study Design
The study was a hospital-based, non-interventional, prospective, cross-sectional study conducted at

Selection Criteria
All new OPD patients of any age and gender on a psychiatric prescription and those consented to participate in the study were included. Patients who refused to participate and prescriptions that did not contain any psychotropic drugs were excluded.

Data Collection Method
The data collection method was individual consultations. All participating patients received a patient information card, and informed consent was obtained in their native language. Data were collected through direct observation in a specially designed form containing relevant details such as patient demographics, prescription information, diagnosis, and prescription details-hospital prescription number, date, medication number, generic names/individual brand names and any fixed-dose combinations (FDCs) prescribed.

Sample Size
The sample size was determined using Eq. 1 (16). Where n is the sample size, z is the standard deviation and is fixed at 1.96 for a 95% Confidence interval, Ɛ is the desired level of precision (i.e., the margin of sampling error tolerated), and is fixed at 5% (0.05), p is prevalence.
No previous studies related to DUR

Data Analysis
For measuring WHO core prescribing indicators, WHO /INRUD (International Network of Rational Use of Drugs) guidelines were followed (17). To assess the rational use of drugs, the mathematical model developed and validated by Zhang and Zhi (18) was applied to appraise medical care comprehensively. This method was used in various medical and health research, called the Index of Rational Drug Prescribing (IRDP) (19). There are five indicators of rational drug prescribing from which the optimal prescribing indicators were defined. Prescriptions with five or more drugs were defined as polypharmacy. These five prescribing indicators (prescriptions including antibiotics, polypharmacy prescription, prescriptions including injection, drugs prescribed by generic name, and drugs prescribed from National List of Essential Medicines of India (NLEM) (19) had the same optimal index of 1. A prescription is considered more rational;

Statistical Analysis
Standard prescriptions, patient care, and facility-specific indicators were used for data analysis. Data reliability was ensured by following WHO guidelines and methods (17). The results are presented with descriptive statistics such as percentages, ratios, or averages. The data was recorded and evaluated with Microsoft Excel 2007.

Characteristics of Study Participants
A total of 655 prescriptions were analyzed. The total numbers of Male and Female participants were 54.96% and 45.04%, respectively. Most psychiatric illnesses (27.79%) were observed in the age group of 21 to 50 years in both sexes. The relative distribution of different psychiatric disorders in diverse age groups and Genders is shown in Table 1.

The Pattern of Psychiatric Disorders
The percentage of prescriptions for schizophrenia, bipolar mood disorders, major depression, anxiety disorders and alcohol-related disorders were 37.86%, 4.88%,11.30%,10.23% and 18.78% respectively.
Psychiatric illnesses like erectile dysfunction, premature ejaculation, panic disorders, neuropathy, sleep disturbances, seizure disorders, ADHD, internet addiction, stress-related disorders, dementia/alzheimer's disease, other substance abuse, mental retardation, post-stroke sequelae, and personality disorders -were grouped as 'other psychiatric illnesses (16.95%). The morbidity pattern and sex difference among different psychiatric illnesses are summarized in Table 2.

Analysis of Prescription Patterns According to Various WHO / INRUD Drug Use Indicators
The 655 prescriptions contained a total of 1691 drugs. Out of these, 1074 were psychotropic drugs.
The other drugs commonly co-prescribed were Vitamin D3, Vitamin B12, Ursodeoxycholic Acid, Melatonin, Benfotiamine, Pantoprazole, Calcium, Silymarine, and Multivitamins/Multimineral. There was no prescription for more than five drugs.

Index of Rational Drug Prescribing (IRDP)
The overall IRDP of the present study was 3.87, with an optimal level of 5 ( Table 5). The overall IRDP of 3.87 was made up of adding the index of antibiotic 1, index of polypharmacy 1, index of injection 1, index of generic name 0.39, and drugs from NLEM 0.48 (19)(20)(21).
Many studies have shown similar results of male preponderance (4,6,7). The reproductive age group  years) accounted for the majority (73.74%) of all psychiatric disorders, as has been seen in many other studies (4,6). In this study, schizophrenia and other psychoses were the most common diagnosis, followed by alcohol-related disorders, depression, anxiety disorders and bipolar mood disorder (Table 2). Piparva et al. (7) have found that schizophrenia was the most common diagnosis, followed by depression whereas, in this study, alcohol-related disorder came in second with a male preponderance, with the age group of 21-50 years.

Analysis of Prescriptions as per the WHO/INRUD Drug Used Indicators
The average number of prescription drugs was 2.58, which was similar to other studies (4,6,7  (25). 48.49% of the drugs were prescribed by the National Essential Medicines List of India 2022. The main goal of the NLEM is to promote the rational use of medicines, considering three important aspects: cost, safety, and effectiveness. In addition, it will also encourage the prescription of drugs with their generic names (26).

Observed Prescription Pattern in Schizophrenia
In our study, the most commonly prescribed drugs were atypical antipsychotics (89.73%), olanzapine (36.98%), followed by risperidone (32.87%) in comparison with typical antipsychotics (10.27%). No single prescription was observed for clozapine and ziprasidone in the study group (Figure 1). In diagnosed schizophrenia and other psychoses, lorazepam (63.93%) was prescribed, followed by clonazepam (13.93%).
Guidelines for the rational use of benzodiazepines recommend short-term use (maximum 4 weeks) or intermittent treatments with minimally effective doses, which should be prescribed only for severe symptoms. (27). Some studies found that first-generation drugs are just as useful as second-generation drugs, except for clozapine, which is superior to all of them (28). Jones PB et al. concluded that initiating treatment with typical rather than atypical antipsychotics in people with schizophrenia whose medication was changed due to intolerance or inadequate response over one year had no adverse effects on quality of life, symptoms, or related outcomes associated with care costs (29). In patients with chronic schizophrenia, olanzapine was more effective than the other drugs tested, and no significant differences in effectiveness were found between the conventional drug perphenazine and the other second-generation drugs.
Olanzapine has been associated with increased weight gain, HbA1C, cholesterol, and triglycerides and has been responsible for metabolic syndrome (30). The 2010 National Institute of Clinical Excellence (NICE) guidelines suggested that it is not necessary to prescribe an "atypical" drug as a first-line treatment, and clozapine can only be offered after the primary failure of two antipsychotics (31).

Observed Prescription Patterns in Bipolar Mood Disorders
For bipolar mood disorder, Divalproex was prescribed most frequently (23.53%). Lithium was found in only one prescription. Second-generation antipsychotics prescribed were olanzapine (29.

Observed Prescription Pattern in Major Depression
Among the antidepressants, escitalopram (41.25%) was the most commonly prescribed drug, followed by mirtazapine (21.25%) and amitriptyline (8.75%). Overall, SSRIs (65%) were prescribed more often than TCAs (8.75%). This is consistent with current recommendations (APA guidelines) and practices for treating Sciences of Pharmacy
In general, benzodiazepines should be avoided and used only briefly in times of crisis (36). Combining a benzodiazepine with an SSRI may provide faster anxiety control, reduction in SSRI-induced anxiety or agitation that may occur early in treatment, better antidepressant adherence, and better control of episodic or situational anxiety in response to specific stimuli. These benefits must be weighed against the potential risks of combination therapy, including side effects, drug abuse, and potential worsening of depressive symptoms(37). Alprazolam and lorazepam were not used for anxiety disorders, as evident from the prescriptions in this study.

Observed Prescription Patterns in Alcohol-Related Disorders (ARDs)
In this study, the incidence of ARDs was high (18.78%). Chlordiazepoxide (39.33%) was the most commonly prescribed antianxiety drug for ARD, followed by oxazepam (12%), lorazepam (7.33%), and atypical antipsychotic olanzapine (10%). Other drugs commonly prescribed for ARDs were ursodeoxycholic acid, baclofen, acamprosate, and pantoprazole. Alcohol use has increased globally, with varying trends in different parts of the world, and has been identified as one of the ten leading risk factors for the burden of disease. There have been a series of global initiatives to reduce the harmful use of alcohol, including WHO's global strategy to reduce the harmful use of alcohol (38).
Central anticholinergic drug trihexyphenidyl (a few Benhexol) was prescribed in various psychiatric illnesses and was found to be the maximum in schizophrenia (75.44%). They are recommended to avoid extrapyramidal side effects (EPS) associated with typical antipsychotics. In schizophrenia, the prescribing frequency of atypical antipsychotics (57.86%) was higher than the typical one (11.91%), and most patients were prescribed anticholinergic agents. Co-prescribing of anticholinergic drugs may add to new or additive adverse effects (e.g., dry mouth, blurred vision, constipation), further reducing the quality of life. As routine use of anticholinergic agents adds to the complexity, side effects, and expenses, whether they should be prescribed routinely or reserved for the cases of overt EPS remains open to question (7). WHO does not recommend anticholinergics to be used routinely for preventing EPS in psychotic disorders treated with antipsychotics. Short-term use of anticholinergics may be considered only in individuals with significant EPS when dose reduction and switching strategies have proven ineffective or when these side effects are acute or severe (39).
FDCs have advantages and disadvantages, susceptibility for EPS differs from person to person, and not all patients require the addition of trihexyphenidyl to overcome EPS. Moreover, the antipsychoticanticholinergic combination does not permit the need-based dose titration of trihexyphenidyl. This could cause additional peripheral and central anticholinergic side effects in the patients, and the long-term use of trihexyphenidyl may cause cognitive impairment and tardive dyskinesia (39).

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Saikia H (2023) -10.58920/sciphar02030042 https://etflin.com/sciphar 51 An interesting case has come to light in which a 14-year-old boy with internet addiction disorder (IAD) was counseled with behavioral therapy. Cognitive behavioral therapy shows promising results in IAD.
Methylphenidate reduces internet usage time in children with IAD co-existing with ADHD (40). However, there is still no consensus on which treatment to offer first.

Conclusion
In this study, the use of psychotropic drugs for different indications followed current guidelines despite the low prevalence of generic prescribing. There is no gender and age difference in prescribing pattern. No polypharmacy was seen, and the use of FDCs was also less. Antianxiety drug lorazepam was extensively prescribed in almost all types of psychiatric illnesses, with a maximum percentage in anxiety and schizophrenia. Rational use of Benzodiazepines requires attention in terms of dose and duration. Atypical antipsychotic olanzapine was more frequently prescribed. Prescribing frequency and pattern of the central anticholinergic drug were similar to antipsychotic drugs irrespective of typical or atypical. Routine use of trihexyphenidyl along with atypical antipsychotic drugs is not justified. The increasing number of alcoholrelated disorders in young adults is also a great concern. DUR is an effective tool to promote rational drug prescribing. Despite all the limitations, such as small sample size, shorter study duration, single study center, etc., the study may be an eye-opener for the healthcare provider. Conducting similar studies on larger study populations will further strengthen the database regarding the drug utilization research of psychotropic drugs.

Funding
Not applicable