Bipolar disorder (BD), also known as bipolar affective disorder, is a clinically highly disabling, complex, chronic mood disorder characterized by intermittent, recurrent episodes of depression and mania/mild hypomania, which can be classified as either bipolar I disorder (BD-I) or bipolar II disorder (BD-II) based on its clinical manifestations [1]. The lifetime prevealence of BD has been estimated to be 1%-2%, with the lifetime prevalence of BD-type I and BD-II being approximately 0.5% and 1.5%, respectively [2,3]. Due to the chronic course of BD, the results of long-term prospective clinical follow-up studies have shown that the percentage of remission in patients with BD-I is even lower: the 4-year remission rate is about 28%, and the 5-year remission rate is about 10% [4,5]. In addition, a long-term observational study of BD suggested that after the first manic episode in 53 BD patients, the relapse rate was about 53.3% within 1 year, and it took about 7.9 months from remission to relapse [6]. The clinical manifestations and course changes of BD are not specific, and the lack of attention to chronic disease management and medication during the maintenance period of BD is highly likely to lead to the relapse or recurrence of BD, which impairs their social functions and increases the socioeconomic burden [7].

BD is a psychiatric disorder that requires maintenance treatment. Currently, the primary treatment is antipsychotic medication, which is the cornerstone of treatment for mental spectrum disorders [8]. As early as 1949, John Cade, an Australian psychiatrist, published a study suggesting that lithium was effective in the treatment of mania, and lithium has been used as a mood stabilizer in the long-term maintenance treatment of patients with BD for nearly 60 years [9]. Antipsychotics are usually categorized as first generation (typical, classical) antipsychotics (FGAs) and second generation (novel, atypical) antipsychotics (SGAs) [10]. Different antipsychotic medications have different mechanisms of action. Many of the medications recommended by guidelines for the treatment of acute manic or depressive episodes have relapse prevention properties. For acute manic or mixed episodes, all guidelines recommend the use of SGAs, such as aripiprazole, quetiapine, risperidone, asenapine, and cariprazine [11]. Lithium or valproate is also frequently used in combination with SGAs, especially in manic episodes with psychotic symptoms, severe agitation, or prominent mixed features. For acute manic episodes, lithium, valproate, and SGAs can all be used as first-line treatment drugs. Monotherapy may be sufficient if manic symptoms are mild; however, combination therapy is recommended if symptoms are severe and accompanied by significant destructive behavior [12]. For bipolar depression episodes, recent guidelines recommend the use of specific SGAs, such as quetiapine and olanzapine/fluoxetine combination [11]. For patients with mild symptoms, lamotrigine and lithium can be considered [12]. Guidelines are cautious about the use of antidepressants (such as selective serotonin reuptake inhibitors, venlafaxine, or bupropion), which are only allowed for careful monotherapy in patients with BD-II and no rapid cycling [12]. For maintenance treatment, lithium is generally recommended by guidelines if there are no contraindications and the patient can tolerate it [11]. Olanzapine is recommended for patients with significant manic episodes, while lamotrigine is recommended for patients with predominant depressive episodes. Most guidelines suggest considering the relapse prevention properties of drugs when choosing the initial treatment for acute manic episodes [11]. In general, medications that are effective in the acute phase of treatment should be continued in the maintenance phase; however, there are some exceptions, such as the efficacy of combination antidepressants that have not been systematically evaluated in large double-blind, placebo-controlled trials; therefore, the long-term use of antidepressants is not recommended, especially given the risk of recurrence of transitions and mood instability that they may cause. However, discontinuation of antidepressants (e.g., fluoxetine) in patients who have responded to combination therapy and are stable may lead to fluctuations in their condition [13].

Several studies on the medication patterns of needle BD patients have been published internationally [14,15]. The studies cover three main areas: clinical medication pattern description using the type and number of psychotropic medications as a reference indicator, research and evaluation of antipsychotic adherence, and comparative studies of different antipsychotic prescribing patterns. With the gradual emphasis on clinical medication standardization in recent years, research scholars and clinical experts in China have begun to carry out studies related to medication patterns. However, there is still a lack of relevant studies, so the present study was conducted to investigate the medication pattern and safety in patients with BD.

This study analyzed the use patterns and safety of antipsychotic drugs in 150 BD patients, who were divided into three groups according to the use of antipsychotics: typical antipsychotics only, atypical antipsychotics only, and concurrent use of both antipsychotics. The results showed that there was a statistically significant difference between the three groups in terms of the number of antipsychotics used and the percentage of anticholinergics used (p<0.001), while there was no statistically significant difference in the percentage of other adjunctive psychotropic medications or the percentage of the use of traditional Chinese medicines (p>0.05). During the follow-up period, all three groups of patients had symptoms of somatic discomfort, cognitive impairment, memory loss, and decreased attention, but the difference in their incidence was not statistically significant (p>0.05). Moreover, none of the three groups of patients had impairments of liver and kidney functions during the follow-up period.

BD is a recurrent mood disorder [16], usually characterized by both manic or hypomanic episodes and depressive episodes, in which the incidence of suicide is 20-30 times higher than that of the general population [17,18], and the emergence and development of this phenomenon is associated with a triad of biopsychosocial factors [19]. The process of suicide involves the development of suicidal ideation, a suicide plan/attempt, and a final suicidal act/attempt [20].

The application of SGAs, such as olanzapine and risperidone has improved the quality of life of billions of BD patients around the world and is widely used in clinical practice, but antipsychotics have limitations in the treatment of negative symptoms and improvement of cognitive functioning [21], and they have a significant glycemic-lipid metabolic adverse effects on glucose-lipid metabolism, causing overweight or obesity and leading to poor treatment adherence. Clinical studies have shown that patients treated with antipsychotics generally have the earliest disappearance of positive symptoms, while negative symptoms and cognitive functioning resolve more slowly. Negative symptoms refer to diminished or absent mental functioning, including diminished emotional expression, social avoidance, lack of social interest, and cognitive functioning (decreased attention and learning ability, and impoverished speech). Studies have shown that a portion of antipsychotic medications can produce a portion of negative symptoms while ameliorating positive symptoms [22], and that the negative symptoms may stem from the inhibitory effects of antipsychotic medications on the mesolimbic-cortical dopamine pathway or 5-HT.

In this study, the basic characteristics of BD patients and the number and type of psychotropic medications used by the patients were described using BD patients attending the hospital. The results showed that antipsychotics played an important role in the pharmacological treatment of BD patients, and both typical antipsychotics and atypical antipsychotics were widely used as the first-line antipsychotics in clinical practice, and were mainly used as a single medication; adjunctive psychotropic medications including anxiolytics, anticholinergics, antidepressants, antimanics, and sedatives and hypnotics were often used to alleviate specific clinical symptoms and some side-effects of antipsychotics, which are often used to alleviate specific clinical symptoms and certain side effects of antipsychotics, and Chinese herbal medicines are also used more frequently. Patients prescribed atypical antipsychotics had a lower rate of comorbid use of adjunctive psychotropic medications than typical antipsychotics.

Earlier, there were antimanic and antidepressant drugs, but the efficacy of traditional medications for manic or depressive episodes of BD was not certain, and even transphasia of morbid affect occurred, i.e., mania became depression. However, lithium has been clinically found to control both manic excitation and often alleviate depression when treating BD. The class of medications known as mood stabilizers has evolved in recent years, and according to the 2000 American Consensus Guidelines [23], mood stabilizers should 1) be effective in treating acute mania/depression and preventing subsequent manic/ depressive episodes, 2) don’t worsen the state of mind or acute episodes, and 3) don’t increase the potential for affective shifts or cyclic changes. Currently, mood stabilizers contain lithium salts and newer anticonvulsants (valproate, carbamazepine, lamotrigine, etc.), while many atypical antipsychotics (quetiapine, olanzapine, risperidone, etc.) have also been listed as candidates for mood stabilizers [24]. The first treatment guidelines for BD were published by the APA in 1994, and our guidelines for the prevention and treatment of BD were published in 2007 [25] and updated in 2014 [26], whereas the Canadian Network for Mood and Anxiety Treatment (CANMAT) has been updated to the 5th edition to date after the first publication of guidelines for BD in 2005 [13], with the last three updates made by the CANMAT in collaboration with the International Society for Bipolar Disorder (ISBD).

The results of the study showed that the clinical use of typical and atypical antipsychotics varied in different regions, which was largely subject to the degree of sample coverage, the level of local economic development, the level of medical development, and other factors. In addition, a study by Wang et al. [27] concluded that antipsychotics combined with adjunctive psychotropic drug use is more common, which is also consistent with the proportion of patients treated with antipsychotics who were also prescribed adjunctive psychotropic drugs in this study. There are no studies on the prescribing of herbal medicines by patients, and the inclusion of the prescribing of herbal medicines in this study was done to provide a more comprehensive picture of the drug therapy of patients with BD.

The innovation of this study lies in the detailed analysis of the use patterns of antipsychotic drugs in BD patients, revealing the differences in the actual clinical application of different types of antipsychotic drugs and their impact on patient safety and efficacy. Especially in terms of the proportion of anticholinergic drug use, we found that patients using only atypical antipsychotics had a lower rate of anticholinergic drug use than those using typical antipsychotics, which provides a new reference for clinicians when choosing antipsychotic drugs. In addition, this study systematically analyzed the use of traditional Chinese medicine in the treatment of BD patients for the first time, providing data support for the integrated traditional Chinese and Western medicine treatment of BD. These findings not only enrich the clinical research data on BD treatment but also provide new ideas for future research directions.

However, this study also has some limitations. First, the difference in the number of participants among the three groups is too large, which may cause bias in the results. For example, the small number of patients using only typical antipsychotics may have affected the power of the statistical analysis and the generalizability of the results. Second, due to differences in economic development levels, investment in medical service resources, drug prices and accessibility, patient characteristics, and physician expertise across different regions, the results of this study cannot represent the use of antipsychotics by BD patients in other regions of China. In addition, the sample size of this study is relatively small, and a convenience sampling method was used, which may affect the generalizability of the results. Future studies should consider increasing the sample size and using a more random sampling method to improve the reliability and generalizability of the research findings.