The prevalence of depression and the number of antidepressant prescriptions have increased globally annually, highlighted during the COVID-19 pandemic when depression and anxiety rates increased significantly in the hardest-hit regions [10]. Similar trends were observed in Taiwan, China [11], the UK [12], and Slovenia [4]. In this study, over five years, both the number of depression diagnoses and antidepressant prescriptions generally showed a fluctuating upward trend. In particular, the third year saw the lowest figures, coinciding with the epidemic's peak. During this period, China's stringent lockdown measures to curb the spread of the virus restricted hospital visits, leading to a temporary reduction in both diagnosed cases and prescriptions. However, the post-pandemic period saw increased medical consultations and antidepressant drugs, likely due to the compounded effects of unemployment, family conflicts, and increased stress from lifestyle changes. Richards-Jones L et al. indicated that participants felt frustrated and isolated during the COVID-19 pandemic because of the blockade[13]. The study also found that the prevalence of depression in women was 1.76 times higher than in men, a ratio consistent with findings from Slovenia [4] and other European studies [14]. This gender disparity can be due to various factors, including biological differences, social roles, cultural expectations, and exposure to violence, abuse, or discrimination [15].
The most used antidepressants in this study were citalopram, escitalopram, and sertraline. These drugs, all SSRIs, are recommended as first-line medications for depression due to their efficacy, tolerability, and ability to reduce recurrence, according to evidence-based guidelines [1]. In contrast, TCAs such as doxepin and clomipramine were the least used. Despite their effectiveness, TCAs are associated with serious cardiotoxicity and anticholinergic side effects, leading to decreased patient tolerance and a decrease in their clinical use, gradually replaced by newer drugs [16].
Over five years, the structure of antidepressant usage shifted, with a decrease in the use of citalopram and escitalopram and an increase in newer antidepressants such as agomelatine and vortioxetine. This trend mirrors the findings of another Chinese study [17]. Agomelatine, which targets the melatonin receptor 1A/1B and the 5-hydroxytryptamine 2C receptor, offers unique benefits in improving mood and cognitive functions and regulating sleep and biorhythms [18]. Vortioxetine, introduced to the Chinese market in 2017, has been prescribed increasingly due to its multimodal action and significant benefits in cognitive functions and depressive symptoms in adult patients with major depressive disorder (MDD) [19].
However, flupentixol/melitracen, a compound preparation known for its anxiolytic and antidepressant properties, ranked fifth in frequency in this study, a decrease from previous studies where it ranked first [5]. This decline is attributed to its limited approval outside China and the need for international evidence-based medical support and clinical consensus [20, 21]. Furthermore, it is not routinely recommended in China due to potentially severe side effects such as tardive dyskinesia and high withdrawal responses [1]. The use of antidepressants varies between different age groups. Sertraline was the most used antidepressant among adolescents, accounting for nearly 41.96% of all prescriptions in this age group. Known for its efficacy in mild depressive disorders and minimal adverse effects, sertraline is the recommended medication for children and adolescents according to Chinese guidelines [1]. Although fluoxetine is the only antidepressant clinically proven to have benefits that outweigh risks for children and adolescents globally [23], it was prescribed significantly less frequently (2.01%) compared to a UK study (38.3%) [12].
Bupropion and fluvoxamine were also widely used among adolescents, likely because bupropion is well-tolerated and effective for mood disorders and ADHD [24], while fluvoxamine is effective against anxiety, improving symptoms in adolescents [25]. Although vortioxetine usage among adolescents is high, the clinical evidence supporting its efficacy and safety in this group remains insufficient [26]. Venlafaxine and milnacipran are popular in adult patients due to their dual-receptor-blocking properties. Venlafaxine is known to improve prognosis and reduce residual symptoms in depression [27], and milnacipran is known for its benefits in treating chronic pain [28]. Agomelatine is also widely used in adults, particularly for its ability to improve sleep parameters, such as reducing sleep latency and nocturnal awakenings [29].
Citalopram and escitalopram are preferred among older patients due to their safety profile and effectiveness, as recommended by the guidelines [1]. Mirtazapine significantly improves sleep and appetite without significant cardiovascular or cholinergic side effects and is frequently prescribed to older adults [30]. Additionally, trazodone is commonly used for its sedative properties, effectively treating moderate anxiety and insomnia in older adults [31].
The use of antidepressants varies significantly between sexes. Paroxetine, which is known to affect a woman's fertility adversely, is less commonly used by women [32]. In contrast, mirtazapine and bupropion, which are associated with lower sexual side effects, are prescribed more frequently to men [32]. Fluvoxamine, which has been shown to alleviate prostate pain, tends to be favored by male patients [33]. Venlafaxine, associated with increased prolactin levels and a greater risk of breast development and cancer, is used less frequently by women [34].
In contrast, women use fluoxetine more frequently, probably due to its efficacy, lower risk of weight gain, and better overall tolerance [6, 35]. The gender-specific usage patterns of other drugs, such as citalopram, flupentixol/melitracen, and agomelatine, require further study. Similar findings on gender differences in antidepressant preferences were observed in a 2021 Italian study, which reported higher rates of fluvoxamine and bupropion use among men under the age of 65 years [6].
A significantly higher proportion of depressed patients received antidepressant monotherapy (76.51%) compared to polytherapy. This preference for monotherapy is consistent with general medical guidelines that recommend single-drug treatment unless the patient does not respond adequately to initial therapies. The complex pathogenesis of depression often coexists with symptoms such as insomnia, anxiety, emotional agitation, or psychotic features, prompting the symptomatic use of various psychotropic drugs. For example, anxiolytics are added for severe anxiety. In contrast, second-generation antipsychotics are utilized as adjuncts to enhance antidepressant efficacy in cases of treatment-resistant depression or depression with psychotic features.
In this study, we could not access individual patient characteristics such as disease severity, regression, and adherence. Future research will aim to gather detailed data on patient demographics and doses to analyze medication changes during the acute and stable phases of treatment. These studies will further assess the impact of the epidemic on antidepressant prescribing behaviors.