INTRODUCTION
Suicide is a serious public health problem that causes approximately 0.8 million deaths every year worldwide [1], and South Korea had the highest suicide death rate among Organisation for Economic Cooperation and Development member countries in 2022 [2]. Suicide is an important medical and social problem in Korea. According to a suicide survey conducted by the Ministry of Health and Welfare in 2018, 18.5% of the Korean population has thought about suicide, and 2.4% have actually attempted suicide [3]. Suicide ranks sixth among the causes of suicide death among Koreans in 2022, and ranks first among the causes of death among those in their teens, 20s, and 30s [4]. Previous research conducted in Korea estimated that annual suicides result in socioeconomic costs of up to 3.0856 trillion won [5]. Suicide can be said to be a very important medical and social problem in Korea.
Meanwhile, many of those classified as high risk for suicide have mental illness. As a result of previous psychological autopsy studies, it was reported that more than 90% of all suicide deaths suffered from mental illness [6]. Although there are conflicting prospective studies, bipolar disorder, major depressive disorder, and schizophrenia are generally considered to have the highest risk of suicide among major mental disorders [7]. Therefore, providing evidence-based psychiatric treatment for these major mental disorders is essential to reduce the high suicide rate in Korea.
When treating people at high risk of suicide, failure to provide evidence-based medical treatment can lead to various risks, such as insufficient treatment response or increased suicide risk [8]. If evidence-based medical care is not secured, there is a possibility that psychosocial stress and coexisting mental disorders in high-risk groups for suicide may be inappropriately managed, which may further worsen the risk of suicide [9]. Additionally, failure to utilize evidence-based approaches to address suicide may result in missed opportunities for early intervention and prevention [10]. However, in actual clinical practice, treatment to prevent suicide in psychiatric patients is sometimes based on the clinician’s personal experience or values rather than evidence-based treatment. To solve these problems, the development of evidence-based treatment guidelines is necessary.
The impact of individual psychiatric treatment on suicide risk in major mental disorders is a complex issue in reality [11-14]. In particular, studies on changes in suicide risk during antidepressant treatment are inconclusive and sometimes contradictory [14-19]. In addition to antidepressants, studies using real-world data have shown contradictory results for other psychiatric drugs as well [20-28]. As a result, in actual clinical practice, the treatment of doctors of psychiatric patients at high risk of suicide are not standardized and can largely be dependent on the clinicians’ individual experiences and values.
Various evidence-based treatment guidelines have been developed overseas to reduce the risk of suicide in psychiatric patients. However, there are still no standard treatment guidelines for psychiatric treatment to reduce suicide in psychiatric patients in Korea. Accordingly, our research team developed evidence-based clinical practice guidelines to recommend treatments for psychiatric patients to reduce suicide that are appropriate for the circumstances of Korea, ultimately contributing to the reduction of suicide risk in Korea.
The goal of this study is to review the latest guidelines on treatments to reduce suicide risk for psychiatric medical staff treating patients with psychiatric disorders, and to develop and disseminate evidence-based clinical practice guidelines appropriate for domestic circumstances. The clinical practice guidelines target patients with psychiatric disorders among those who require management of suicide risk, and include both psychiatric pharmacological treatment and non-pharmacological treatment for adults and children. Doctors who treat psychiatric patients at various medical institutions in Korea, including private clinics, hospitals, and university hospitals, were considered as expected users of the treatment guidelines.
METHOD
Forming a development group
This clinical practice guideline was developed mainly by the participating researchers of The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS) [29], a national research project conducted under the sponsorship of the National Center for Mental Health under the Ministry of Health and Welfare of the Republic of Korea. The development committee of this clinical practice guideline was composed of researchers from K-COMPASS, and was overseen by professors of psychiatry and preventive medicine, who led the development methodology. The development committee developed key questions (KQs), searched the literature, evaluated the retrieved literature, and developed draft recommendations. In cooperation with the external advisory committee, development committee were responsible for improving the completeness of the treatment guidelines and ensuring that opinion gathering through Delphi was carried out. Meanwhile, psychiatry specialists working at university hospitals, hospitals, and private clinics participated in the advisory committee of this research. They participated in Delphi rounds regarding the KQs developed by development committee and contributed to reaching a consensus. It was confirmed that there was no external influence, including from the government and public institutions, throughout the treatment guideline development process. Members of the development committee signed a conflict of interest declaration before developing and consulting on the guidelines. This conflict of interest declaration included whether there was a commercial interest related to the practice guideline. All authors have confirmed that they have no conflicts of interest.
Determination of development method, scope of treatment guideline, and KQs
Several guidelines for psychiatric treatment to reduce suicide risk have been developed overseas, but as of 2024, none have been developed domestically. The development committee decided to accept and adapt treatment guidelines developed overseas. In this paper, the research team described the process of selecting and applying existing guidelines for suicide risk groups based on the ADAPTE methodology [30] and the Korean Medical Association’s Clinical Practice Guidelines Acceptance and Adaptation Manual [31] developed based on the ADAPTE.
The ADAPTE methodology provides a systematic approach for adapting existing clinical practice guidelines to a local context, ensuring that they are relevant and applicable to the specific healthcare environment. This methodology involves three main phases: setup, adaptation, and finalization. During the setup phase, the need for adaptation is established, a guideline adaptation team is formed, and the scope and purpose of the guidelines are defined. The adaptation phase involves identifying and retrieving existing guidelines, assessing their quality using the AGREE II instrument [32], and deciding on necessary adaptations to fit the local context. This includes modifying recommendations to address local healthcare practices, cultural factors, and resource availability. Finally, in the finalization phase, the adapted guideline is drafted, validated through expert reviews and consensus methods such as the Nominal Group Technique (NGT) and Delphi method, and prepared for implementation.
For this practice guideline, the development committee developed KQs according to the Patient, Intervention, Comparison, Outcome format. In this process, a total of eight working-level meetings of the development committee were held starting on July 3, 2023. A total of 4 KQs were developed at the beginning of development, and these were subdivided into 33 questions (23 questions for drug treatment, 10 questions for non-drug treatment), and finally compressed into 10 questions (6 questions for drug treatment, 4 questions for non-drug treatment).
Search and selection of treatment guidelines
We searched domestic and international databases such as PubMed, Cochrane, Ovid-Medline, EMBASE, KoreaMed, Guideline International Network, National Institute of Health and Care Excellence, and Korea Medical Citation Index at the Chung-Ang University Medical Library. A search strategy was developed and applied for each search data source using “Mental disorder AND Suicide AND therapy AND guideline” as the basic index word. Among these, the working committee excluded documents that were duplicated or met the exclusion criteria. The inclusion criteria were evidence-based practice guidelines containing information on the quality of evidence and strength of recommendations, practice guidelines addressing pharmacological and non-pharmacological treatment of mental health, and practice guidelines written in English or Korean. Exclusion criteria included clinical guidelines written by a single author who lacks representation, clinical guidelines published without references, clinical guidelines targeting only specific population groups (e.g., children, adolescents or the elderly), and clinical guidelines dealing with intentional self-harm other than suicide (Table 1).
Evaluation of treatment guidelines
The quality of the treatment guidelines was evaluated using the AGREE II tool [32]. Four people in the development committee evaluated each treatment guideline, and if there was a difference in scores of more than 4 points for the same item between evaluators, a reexamination process was performed. Treatment guidelines that received a score of 60% or higher in the stringency area of development in the AGREE II evaluation were selected.
To assess the recency of the selected practice guidelines, we checked the publication year of the practice guideline and the date when the latest evidence was searched. If the development committee judged that individual KQs needed to be updated, the latest literature published until February 2024 was additionally searched and reflected in the guidelines.
In order to evaluate the acceptability and applicability of the treatment guidelines, Korea’s health insurance system, treatment accessibility, and medical culture were considered as well. The selected treatment guidelines were generally found to have no problems in terms of acceptability and applicability. Moreover, the development committee performed additional judgement for each recommendation whether it was acceptable or applicable to the medical environment in Korea.
Preparation and approval of recommendations
Level of evidence and recommendation grade system
The level of evidence and recommendation grade of this practice guideline were determined by referring to the “Evidence-based guideline for depression in primary care” developed by the Korean Academy of Medical Sciences in 2022 [33]. The level of evidence and recommendation grade are presented in Table 2.
Process of deriving recommendations
The working committee drafted recommendations based on KQs from the selected practice guidelines. The development committee adopted an approach using the NGT to review the recommendations of the practice guidelines. NGT is a formal decision-making technique that structures interactions within a group [34]. A working-level meeting consisting of eight people conducted a consensus process for each recommendation. Each participant spoke in turn about his or her thoughts, and after a short discussion, the level of agreement was assessed. If a consensus of 70% or more was reached, the decision was made to accept the recommendation. Recommendations that required modification, as needed, were revised through the informal consent of the working committee and then changed through approval by the entire development committee.
Preparation and approval of draft treatment guidelines
Based on the recommendations approved by the development committee, the working committee drafted the treatment guidelines. The treatment guideline consists of a summary, introduction, target population and users, development method, and treatment guideline. The development committee reviewed the form and content of the draft in detail and approved it.
Guideline confirmation and review process
A review committee consisting of 11 psychiatric specialists in Korea reviewed and finalized the draft guideline using the Delphi method. A draft of the guideline was circulated via email, along with the development method for this guideline and the evidence for each KQ and recommendation. The first Delphi round aimed to gather expert opinions on the initial draft and to identify areas requiring modifications or disagreements. In the second Delphi round, the revised recommendations were presented to achieve further consensus. A consensus was reached when more than 70% agreement was obtained for each question. If disagreements arose, they were resolved through further discussion and literature review. In some cases, intervention by mediators was used to facilitate agreement. After a total of two Delphi rounds, the treatment guidelines were finalized, and the feedback opinions were reflected and approved by the development committee.
RESULTS
Search and selection of previous treatment guidelines
A total of 4,825 articles were identified from PubMed, EMBASE, Psycinfo, Cochrane library, and Guideline International Network through database searches based on index words. Among these, 121 overlapping documents and 1,355 documents that did not fit the publication type (letter, abstract, review, editorial, response report, and technical note), had single author, or was about other topics than suicide were excluded. The development committee applied the inclusion and exclusion criteria to the remaining 3,349 documents. A total of four treatment guidelines were selected, including VA/DoD Clinical Practice Guideline: the assessment and management of patients at risk of suicide (hereinafter referred to as VA/DoD clinical guideline), published by the U.S. Department of Veterans Affairs in 2024 [35], American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients with Suicidal Behaviors (hereinafter referred to as APA practice guideline) published by the APA in 2004 [36], Clinical Practice Guideline for the Prevention and Treatment of Suicidal Behaviors (hereinafter referred to as Spanish practice guidelines) published by the Spanish Ministry of Health in 2020 [37] and the Brazilian Psychiatric Association guidelines for the management of suicidal behavior (hereinafter referred to as Brazilian practice guidelines) issued by the Brazilian Psychiatric Association in 2021 (Figure 1) [38,39].
Evaluation of previous treatment guidelines
Quality evaluation results of treatment guidelines using the AGREE II evaluation tool.
The AGREE II tool was applied to the four selected guidelines for evaluation, and “Spain, 2020,” “Brazil, 2021,” and “VA/DoD, 2024” were selected for acceptance and development. The average AGREE II scores of the four reviewers of the four evaluated practice guidelines are listed in Table 3. The three selected treatment guidelines all scored more than 60% in the evaluation score for the stringency of development.
Assessing the up-to-dateness of treatment guidelines
To evaluate the up-to-dateness of the three treatment guidelines selected through AGREE II, additional literature up to February 2024 was searched for each KQ. However, KQ2, KQ4, KQ9, and KQ10 were covered in the VA/DoD, 2024 practice guideline, and since a sufficiently up-to-date literature search was performed in this practice guideline, no additional up-to-date literature search was performed. In addition, the results discovered through new literature search on KQ not covered by VA/DoD, 2024 are presented in the Table 4.
Evaluation of treatment guidelines’ contents
We evaluated whether the previously developed treatment guidelines sufficiently included the contents of the newly developed treatment guidelines. It was confirmed that all 10 KQs could be addressed through the three treatment guidelines. The 10 KQs and the scope covered by each practice guideline are presented in Table 5.
Evaluation of acceptability and applicability of recommendations
As a result of evaluating the overall acceptability and applicability of the treatment guidelines, it was found that all treatment guidelines generally had no problems in terms of acceptability and applicability. In addition, for each recommendation, the development committee additionally judged whether it could be accepted and applied to the medical environment of Korea. These standards include health insurance coverage of individual treatments and the results of research on the treatment method performed in Korea. Among these, the recommendation of carbamazepine for borderline personality disorder in the draft of KQ3 was evaluated as not appropriate for the medical situation in Korea. Additional domestic studies that matched the content of the core questions were searched in KQ1, KQ7, KQ9, and KQ10, and the results of these studies were consistent with the recommendations of the previous treatment guidelines. For other KQs, no related domestic research was identified.
Making and approving recommendations
Preparation and modification of recommendations
The working committee drafted recommendations based on KQs from the selected practice guidelines. In the prepared draft, recommendations were modified or excluded based on the recency, domestic acceptability, and applicability of individual recommendations through NGT consensus at the development committee. In the case of KQ3, the original Spanish guideline included a recommendation for the use of carbamazepine in patients with borderline personality disorder. However, in the 2022 Cochrane Review, based on data from 4 clinical trials and 14 databases conducted until February 2022, when individual drug ingredients were analyzed in patients with borderline personality disorder, there were no medications that were shown to be effective [40]. In addition, carbamazepine has side effects such as bone marrow suppression and requires continuous monitoring such as blood concentration and blood cell tests, so it is a drug that is not often used clinically these days in Korea. It was decided, through consensus of the development committee, not to specifically recommend anticonvulsants for personality disorders, including borderline personality disorder. In addition, the Spanish practice guidelines recommended the use of carbamazepine and valproate in bipolar disorder, and in addition to valproate and carbamazepine, the development committee decided to additionally recommend lamotrigine, which is actively used in clinical practice in Korea. In the case of KQ5, according to a meta-analysis of randomized clinical trial (RCT) studies published in 2022, when evaluating suicide-related risks including suicidal thoughts, suicide attempts, and suicide deaths in the high-risk suicide group, the use of first-generation antipsychotic drugs was associated with a high suicide-related risk (5.44; 95% confidence interval [CI] 1.47-20.00), while second-generation antipsychotics were associated with a lower risk of suicide (0.80; 95% CI 0.74-0.86) [41]. The guidelines were revised to recommend overall use of second-generation antipsychotics, not just olanzapine and risperidone, preferentially over first-generation antipsychotics. The recommendations, including the modifications, was then approved by the development committee and referred to the external advisory committee’s Delphi round.
External review and approval of recommendations
Among the recommendations submitted to the Delphi round, recommendation 3 for KQ1, recommendation 5 for KQ2, and recommendation 15 for KQ 9 did not pass the first Delphi round. Recommendation 3 was “Antidepressant treatment is not recommended for adults diagnosed with bipolar disorder and at high risk for suicide”. There were opinions that it was difficult to distinguish between bipolar disorder and major depressive disorder in private clinic. Recommendation 5 was “Lithium and antidepressant combined treatment can be administered to adults at high risk of suicide diagnosed with major depressive disorder.” There was an opinion about the risk of overdose on lithium for suicide purposes. Recommendation 15 was “Individual cognitive behavioral therapy (CBT) can be performed in adults at high risk for suicide.” There was an opinion that CBT is a treatment that requires a lot of human and time resources and is not appropriate for a rapid therapeutic approach in the patients with acute risk for suicide. Reflecting these opinions, the development team added the risks and prevention measures of lithium overdose in recommendation 5, and clinical considerations on the sessions and time of CBT and human and temporal resource consumption in recommendation 15. These changes were supplemented by including them in the main text of the guidelines distributed in booklet form, rather than to individual recommendations. Afterwards, the entire recommendations were approved in the second Delphi round. The final approved KQs and treatment recommendations are shown in Table 6.
DISCUSSION
In this study, foreign treatment guidelines were adapted and modified according to scientific methodology to develop evidence-based treatment guidelines for pharmacological and non-pharmacologic treatment for psychiatric patients in Korea. Through this, clinicians were recommended to treat high-risk groups for suicide appropriate to the Korean sociocultural environment. According to the results of our research team’s search during the development of the treatment guideline, this study is the first that chose the adaptation method among the previous clinical guidelines to prevent suicide in psychiatric patients.
Suicide is a phenomenon that occurs due to the interaction of various psychobiological and social factors, and it is necessary to utilize individual treatment guidelines that take into account the sociocultural environment of each country. In particular, Korea has the highest level of suicide rate in the world, with a very high elderly suicide rate and a less skewed gender ratio between men and women. Since the 1997 financial crisis, economic difficulties such as unemployment, academic pressure, and cultural difficulties such as isolation of the elderly have contributed significantly to suicide [42-46]. Therefore, it is more important to develop treatment guidelines that reflect these characteristics. However, in the search conducted by this research team, there were very few studies including RCTs, systematic reviews, and meta-analyses that addressed the suicide prevention effect of psychiatric treatment in Korea [47-49]. Therefore, it may be an efficient method to adapt treatment guidelines developed overseas with sufficient scientific evidence to fit the Korean situation.
The Korean guidelines for suicide prevention in psychiatric patients were developed by adapting and modifying the guidelines from the United States (VA/DoD), Spain, and Brazil. This adaptation process has several strengths: 1) reviewing the contents of other guidelines ensured that the Korean guidelines are built upon a solid foundation of existing evidence and best practices from around the world, 2) modifying the content to fit the Korean medical reality made the guidelines more relevant and practical for implementation within the local healthcare system, and 3) supplementing any areas lacking in up-to-dateness ensured that the guidelines reflect the most recent advancements in suicide prevention research.
Foreign guidelines provide a comprehensive approach to suicide risk assessment, psychological treatment, and pharmacological interventions. In contrast, the Korean guidelines place more emphasis on tailoring these interventions to the Korean healthcare system and cultural context, ensuring the applicability and effectiveness of evidence-based interventions for high-risk groups within Korea’s unique medical and cultural framework. This includes considerations of healthcare accessibility and insurance coverage in Korea, which differ significantly from other countries.
The treatments recommended with the highest recommendation grade and level of evidence in this guideline were lithium, clozapine, atypical antipsychotic, electroconvulsive therapy (ECT), and CBT. In the Brazilian guidelines, selective serotonin reuptake inhibitors, lithium, and clozapine, and in the Spanish guidelines, antidepressants, clozapine, lithium, and ECT were recommended as treatments with the recommendation grade. In the VA/DoD guidelines, no treatment was recommended at the highest grade. Because our guideline synthesized the literature referenced in previous guidelines, more sufficient literature evidence was obtained for individual treatment recommendation, and through this, a larger number of treatments were recommended at the highest level.
In the case of lithium, the Brazil and Spain guidelines recommended it at the highest level, and the VA/DoD treatment guidelines also recommended use at a low level until the 2019 edition, but from the 2024 revision, the use of lithium is neither recommended nor denied. This is because two meta-analyses published in 2022 gave conflicting results on the effects of lithium [41,50]. However, the suicide prevention effect of lithium has been continuously emphasized in previous papers [51-53]. It also received wide approval in the Delphi consensus among Korean experts. It is not enough to deny the repeatedly reported effect of lithium on preventing suicide in patients with mood disorders, based on only one meta-analysis published in 2022.
In the case of dialectical behavior therapy (DBT), the treatment guidelines in Brazil and Spain recommended its use in adolescents with borderline personality disorder and a history of suicide attempts and self-harm, but the VA/DoD treatment guidelines changed their position from recommending its use in 2019 and did not recommend or object to DBT in 2024. This is because systematic literature reviews published in 2019 and 2021 failed to show evidence that DBT is effective when compared to treatment as usual or psychotherapy [54,55]. However, both of these analyzes have a limitation in comparing DBT with other treatments that are effective in preventing suicide. Other previous studies on the effectiveness of DBT support the use of DBT in these groups [56-59].
In this guideline, the applicability and acceptability of each recommendation in the Korean environment were evaluated. Here, accessibility, including the inclusion of health insurance and the cost of treatment, was evaluated as important. However, since Korea’s medical accessibility is excellent and citizens can use medical services at relatively low prices through the national health insurance system [60], the actual recommendations were not rejected or modified for economic reasons. If additional clinical guidelines are made for those with suicide risk and poor access to medical care, or if medical accessibility worsens or medical costs increase due to changes in the medical system in Korea in the future, the current recommendations may be excluded or modified in the future.
The external advisors who evaluated the clinical usability of this guideline included psychiatrists in private clinics, public health centers, secondary and university hospitals. This was intended to verify the acceptability of these guidelines across various healthcare institutions providing care for high-risk suicide groups. In clinical practice in Korea, treatment for psychiatric disorders is sometimes provided in departments other than psychiatry, but most treatment for patients at risk of suicide is provided in psychiatry. In the future, if doctors from other departments become involved in the treatment of high-risk groups for suicide due to changes in the medical environment in Korea, there is a possibility that doctors from other departments may participate as advisory committee members along with psychiatrists for additional revisions to the guidelines.
There are several limitations in the development process of this treatment guideline. First, it does not include information for screening high-risk groups for suicide, which may lead to confusion about which people this treatment guideline should apply to. However, even people who are not classified as high-risk for suicide by well-made algorithms may attempt suicide [61,62], and psychiatric patients have a higher suicide risk than the general population, so it is fundamental to make evidence-based clinical measures to prevent suicide risk in all psychiatric patients [63,64]. We plan to expand the scope of the treatment guideline to include screening for high-risk groups for suicide in the future. Second, although we selected guidelines published within the last 5 years, some of the literature cited in these guidelines was published as long as 20 years ago. Fortunately, the VA/DoD treatment guidelines announced in 2024 were judged to be sufficiently up-to-date at this point. We additionally conducted a review of the recency of recommendations not covered in the VA/DoD practice guidelines.
To ensure the effective implementation of these guidelines in clinical practice, future efforts should focus on developing comprehensive training programs for healthcare providers, integrating the guidelines into existing electronic medical record systems, regularly monitoring and evaluating the guidelines’ impact on clinical practice and patient outcomes, and implementing specific measures to ensure effective utilization of the guidelines. Additionally, pilot programs could be conducted to refine these strategies and ensure their practicality before wider implementation.
Furthermore, future research should investigate the long-term effectiveness of these guidelines and their applicability to other regions and populations. This would involve longitudinal studies to assess the sustained impact of the guidelines on suicide prevention and examining how these guidelines can be adapted for different cultural and healthcare settings. Such research will help to validate the generalizability and robustness of the guidelines, ensuring that they can be effectively implemented in diverse contexts. Additionally, it is worth considering not only clinical studies to confirm the reduction in suicidal ideation or suicide rates among patients treated in hospitals and clinics, but also evaluating the effect on reducing suicide rates at the community level through interrupted time series analysis.
In conclusion, this study aimed to reduce the high suicide rate in Korea by developing evidence-based treatment guidelines that encompass pharmacological and non-pharmacological treatment for psychiatric patients. To this end, foreign treatment guidelines were adapted and modified according to scientific methodology and applied to domestic circumstances. Ultimately, varioius treatments including lithium, clozapine, atypical antipsychotics, ECT, and CBT were recommended, and the applicability of the guidelines was improved through the experience and consensus of clinicians. This study sought to maximize the effectiveness of suicide prevention for psychiatric patients by presenting evidence-based suicide prevention guidelines that reflect the special socio-cultural environment of Korea, a country with a high risk of suicide worldwide. In the future, we plan to further supplement the treatment guidelines through additional research, such as screening for high-risk groups for suicide.
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