Patterns of Antidepressant Prescriptions for the Treatment of Depression: A Scoping Review

Introduction: Depression is an important global public health problem due to its relatively high lifetime prevalence and signicant disability caused by it. It is associated with functional impairment and high morbidity and mortality. Antidepressant medication is considered to be the best treatment option for depression Method: Literature searches (2000-2019) were performed using PubMed, HINARI and Google Scholar that analyze the pattern of prescription of antidepressants among the patients of depression. . Results: Females suffered from depression more than their male counterparts. Married people, housewives, lower income people, employees and highly educated people suffered more from depression. Selective Serotonin Reuptake Inhibitors (SSRI) like Sertraline, was found out to be the most preferred antidepressant among the depressive patients. Conclusion: Our Study suggested that out of ve major antidepressant drugs being available for the treatment of depression, selective serotonin reuptake inhibitors are preferred over others because of their better side effect and tolerability prole. prescription patterns antidepressants in


Introduction
Depression is a common mental disorder and a major cause of functional disability 1,2 . According to the World Health Organization (WHO), by 2020, it will be the second-highest known cause of worldwide disability 3,4 . Depression is characterized by a sad mood, pessimistic thought, lowered interest in day-today activities, poor concentration, insomnia or increased sleep, signi cant weight loss or gain, decreased energy, continuous feelings of guilt and worthlessness, decreased libido and suicidal thoughts occurring for at least two weeks 5,6 . Depressed patients can be of any gender, age, or background. Due to fear of stigmatization associated with mental disorders, patients lack to seek medical treatment in their early stages [7][8][9] . To maintain normal human health in patients, drugs play a crucial role. Antidepressant drugs are the most widely used and are most effective in the treatment of depression 10,11 . For many years, tricyclic antidepressants (TCAs) have been the drug of choice for treating depression in patients [12][13][14] .
Many new antidepressants with better tolerance and broader indications have been discovered because of an increase in the prevalence of depression throughout the world 15 . This results in the gradual replacement of conventional drugs such as TCAs and monoamine oxidase inhibitors (MAOIs) by SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants 7,16,17 . The most appropriate antidepressants should be selected according to symptoms and patient characteristics, with adequate dose and duration of therapy, to enhance the treatment success rate 18,19 . However, other factors, such as adverse effect pro les, cost, safety pro le, history of prior medication treatment, and patient preference, are important in the initial selection of antidepressants and should be considered by physicians 20,21 . The optimal use of antidepressants could reduce individual distress, along with the social burden of depression 22 . The aim of the analysis of prescribing patterns is to evaluate the prescription habits of medical practitioners and to suggest necessary modi cations if required to make drug therapy rational and cost-effective 6,16 . The use of antidepressants has increased within the last two decades 24 . As a result of the increased prescription and use of antidepressants, the need for information regarding the actual prescribing practices has become vitally important to maintain patient safety as well as to ensure that the optimal therapeutic outcome is achieved, especially when the nature of the side effects of these drugs are considered. Hence, this review aims to investigate and summarize the studies on antidepressant prescription patterns for the treatment of depressive disorders.

Methods
Data Sources, Search, and Selection A comprehensive literature review was conducted using PubMed and Google Scholar. The search was limited to English language articles published in journals between January 2000 and 2019. The search keywords used were depression, drug use evaluation, antidepressants, prescription patterns of antidepressants in depression, SSRIs, TCAs, SNRIs, and atypical antidepressants. We also included articles listed in "related articles" from PubMed and the author's reference lists. To improve the comprehensiveness of the literature, available review articles on the topic were also examined. This review provides a comprehensive review of the available literature.

Data screening and extraction
Study selection (1) The literature on varying methodologies (observational, cross-sectional, retrospective, survey, case reports) analyzes the prescription pattern of antidepressants for the treatment of depression.
(2) Patients irrespective of age and sex with a primary diagnosis of depression and prescription of at least one antidepressant drug.
Our study outcomes were the demographic pro le and prescription pattern of antidepressants among patients with depression. Studies that did not meet our criteria were excluded during the review. Studies were discarded if they were clinical trials and reviews.

Results
The studies included were published between 2000 and 2019. The total sample size was 1,88,713 patients. The studies were conducted in Sweden 25   Sertraline was common in children followed by uoxetine in younger age and citalopram in young adults.
SSRIs were the most common drug in both males and females. SNRIs and other antidepressants (Mirtazapine and bupropion) prescription were most common for young adults and TCAs were more prevalent in 0-11 years female. The majority of the individuals suffering from depressive disorder were married, employees, and housewives with secondary education.

Islam et al., 2019 27
To obtain information regarding the prescribing pattern of antidepressant drugs following WHO prescribing indicators in two teaching hospitals.

Nahas and Sulaiman, 2018 28
To explore the pattern of prescribed antidepressants among depressive men in Malaysia.
Our review showed that the majority of the patients receiving antidepressants for the treatment of their depression were females 27,[30][31][32][33][34][35][36][37][38][39][40][41][42][43] . This could be due to hormones that are associated with the regulation of the menstruation cycle and pregnancy affecting mood in females. These alterations in hormonal regulation cause dysregulation of the stress response, which makes them more sensitive to developing depression and often shows magni ed neuroendocrine responses to even low levels of stress 30,40,41,44 . Women play multiple roles in family and society, such as homemakers, spouses, mothers, professionals, and caregivers. These multiple responsibilities may be the source of increased stress that might have led to depression in them 45, 46. In many societies, until today women are not given equal respect, they are thoughtless powerful with low status, they cannot make a choice, and they are sexually abused, which all results in the development of depression in them 5,44 . In contrast to our ndings, one study reported more depressive males than females, which could be due to more stress at work, a monotonous lifestyle, and lack of entertainment, low income, and economic burden of family 26 . Our review suggests that depression is associated with various psychological factors, such as loneliness, lack of family care and affection, poor family support, insu cient time with children, high use of emotional coping, low level of spirituality, stressful incidents, poor health, and dependency 26,40 . Sedentary lifestyle, lack of physical exercise, lack of hobby, irregular dietary habits, smoking, and taking alcoholic beverages or substance use are also interconnected with depression 26,32,37 . Continuous arguments, stressful daily routines, unsupportive spouses, continuous discouragement, lack of family time or husbands or wives going to other countries for employment, and ignorance from family members may be the reason for more married, housewives, and lower-income people being vulnerable to depression 26,27,30,31,33,37,38,47 . One study 48 showed that a spouse's weekly working hours are greatly associated with the partner's risk of developing depression and suicidal thoughts. This means that long working hours not only affect individuals' own mental health but also affect their spouses 48 . Unsatisfactory job, lower income, level of physical activity, lack of encouragement, job demands, time pressure, promotion, and job security, all of which make an individual lose their con dence; hence, could be the reason for taking antidepressants by a high number of employees involved in paid work 26,31,37 . Similarly, being concerned about more pro t or suffering a continuous loss in their business may also lead to depression in people involved in selfemployed business 30 . Our review showed that education is another source of depression in many people.
Highly educated people become depressed because of not getting their level of work, no place to implement their knowledge and skills in their jobs, more workload but low paid jobs, challenges with high competition in jobs, and lack of growth in the particular job 26,31,33,38 . However, other studies have displayed less educated people as victims of depression 27,37 . These people work as machine operators, laborers, farmers, and unskilled manual workers, where there is more physical and psychological related stress along with less respect from other employees. The prescribing pattern of antidepressants for patients with depression varies across different countries. This could be due to differences in availability and antidepressant prices as well as variations in recommendations in each country's national guidelines 30,38 . Medical treatment of depression not only improves the mental health of patients but also increases their physical and social performance, making them optimistic and encouraged towards life 34 . Our review revealed that SSRIs are the dominant antidepressants prescribed over TCAs, SNRIs, and other atypical antidepressants for the treatment of depression [25][26][27][28][29][31][32][33][34][35][36][37][38][39] . The frequent use of SSRIs could be because of the advantages they offer. Antidepressants other than SSRIs nonselectively inhibit the reuptake of norepinephrine, dopamine, and serotonin into presynaptic vesicles and affect adrenergic, cholinergic, postsynaptic serotonin, and histaminic receptors in the brain, which are unrelated to depression, leading to intolerable adverse effects 49 . SSRIs do not cause life-threatening adverse effects, such as overdose-related cardiotoxicity and CNS toxicity, as they do not have receptor antagonism 50 . Additionally, they can be administered once daily, require less dose titration than TCAs, are safer, and show fewer side effects compared to other antidepressants 28,33,[35][36][37]51 . Hence, it could be safer for many patients. In contrast, a study 30 showed that TCAs are most commonly prescribed despite SSRIs being more advantageous, which could be due to the affordability and easy availability of TCAs over SSRIs. In developing countries, the affordability of drugs plays an important role, where not all people can buy expensive medicines. Many have to rely on government insurance policies to obtain drugs for their treatment. Many people buy antidepressants from the hospital since they are available at cheaper prices than in retail pharmacies. Such regional differences in the use of antidepressants may also contribute to differences in culture, promotional activity, and national income 52,53 . Our review showed that sertraline was the most frequently used SSRI, followed by others such as escitalopram, uoxetine, paroxetine, and uvoxamine. Amitriptyline is commonly used among TCAs, venlafaxine, and duloxetine among SNRIs and mirtazapine, and bupropion among atypical antidepressants.

Conclusion
Our study revealed that the majority of antidepressant users were aged 40-50 years, mostly females, married, housewives, lower-income, and highly educated. SSRIs were found to be highly prescribed antidepressants over TCAs, SNRIs, MAOIs, and atypical antidepressants. Among the prescribed SSRIs, sertraline was the dominant SSRI. Physicians who treat patients with depression should have su cient knowledge of the safety and effectiveness of available medications and should be updated with newer treatment strategies.