Effects of Duration of Untreated Illness on Suicidal Ideation Among Patients With Panic Disorder

Abstract

Objective

Patients with panic disorder (PD) are approximately four times more likely than the general population to exhibit suicidal ideation (SI) and suicide attempts. Although prolonged duration of untreated illness (DUI) is a known risk factor for adverse outcomes in mood disorders, its impact on suicidality among patients with PD has not been well established. This study investigated whether prolonged DUI is associated with heightened SI among patients with PD, considering sociodemographic and clinical factors.

Methods

A total of 804 patients with PD were recruited. DUI was defined as the time between symptom onset and the initiation of psychiatric treatment. Clinical assessments included the Scale for Suicide Ideation (SSI), Beck Depression Inventory-II (BDI-II), and Panic Disorder Severity Scale. Sociodemographic and clinical predictors of SI were examined using independent t-tests, Pearson’s correlations, and multiple regression analysis.

Results

In patients with PD, the mean DUI was 41.56 months. Longer DUI was positively correlated with higher SSI total scores, along with greater depression severity. Gender women, unmarried status, and elevated BDI-II scores were significantly predicted higher SSI total scores. In the multiple regression model, prolonged DUI remained an independent predictor of SSI (B=0.116, p=0.012) after adjusting for other variables.

Conclusion

These findings indicate that delayed treatment contributes to increased suicidality in PD, beyond demographic and depressive risk factors. Therefore, early detection and timely intervention using treatment strategies that enhance awareness, improve the accessibility of psychiatric services, and provide social support may reduce DUI and mitigate suicide risk among patients with PD.

INTRODUCTION

Panic disorder (PD) is characterized by sudden and unexpected panic attacks, persistent worry about the consequences of subsequent panic attacks, or maladaptive behavioral changes to avoid them [1]. Moreover, PD not only results in significant functional impairment, comorbid depression, and reduced quality of life but has also been consistently associated with increased suicidality [2-5]. Patients with PD are nearly four times more likely than the general population to exhibit suicidal ideation (SI) and suicide attempts [6,7]. Previous studies have reported that 47% of patients with PD experience SI, with up to twothirds frequently thinking about death [3,8]. The three-step theory of suicide posits that SI is the first step of suicidality, arising when psychological, emotional, or physical pain exceeds one’s threshold, accompanied by hopelessness that the pain cannot be alleviated, and progressing to suicide attempts if the individual has the capacity to act [9]. A recent systematic review and meta-analysis identified SI as a strong precursor of suicide attempts with mortality risk [10]. Likewise, a large cohort study of patients with PD reported that SI is a key predictor of suicide attempts [11], highlighting the importance of the primary prevention of SI through early detection and intervention as part of preventive medicine.

Duration of untreated illness (DUI)—the time interval from first symptom onset to appropriate diagnosis and treatment initiation [12,13]—has been identified as a critical predictor of severe symptomatology, frequent psychiatric comorbidities, and a worse clinical course in psychiatric disorders [14-18]. A retrospective study demonstrated that prolonged DUI in anxiety disorders, including PD, precipitates impaired functioning (e.g., occupational and social domains) and diminished quality of life, resulting in sociodemographic ramifications, such as medical expenses, living alone, and unemployment [19]. In PD, longer DUI has been associated with greater chronicity [20] and poorer pharmacological prognosis [14,21,22]; specifically, in PD, DUI longer than 12 months is strongly associated with frequent post-onset comorbid major depressive disorder (MDD) [14], a known risk factor for elevated suicidality. Evidently, DUI has emerged as a factor increasing suicidality in affective disorders [23]. As higher suicidality is associated with frequent attacks and the fear of cognitive dyscontrol in PD [9], it can be inferred that prolonged DUI may heighten patients’ perception of losing control, which aggravates SI with increasingly severe symptoms.

Despite these potential implications, few studies have directly examined the relationship between DUI and suicidality in PD. This study aimed to investigate the effect of DUI on SI among patients with PD by considering relevant sociodemographic and clinical factors. Accordingly, we proposed the following hypotheses: 1) both sociodemographic (e.g., age, gender, educational level, employment, income, and marital status) and clinical variables (e.g., DUI and severity of depressive and panic symptoms) are associated with SI in PD; 2) prolonged DUI significantly predicts SI even after adjusting for these factors.

METHODS

Participants

A total of 804 patients with PD were recruited from the Department of Psychiatry at CHA Bundang, Ilsan, and Gumi Medical Centers, from 2006 to 2023. Participants were aged 18–77 years (mean=38.48±11.51 years) and fulfilled the criteria for PD with or without agoraphobia, as outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [1]. Exclusion criteria were a primary diagnosis of any psychosis, including schizophrenia; MDD; anxiety disorders other than PD; other substance use disorders, including alcohol use disorder; neurocognitive or neurodevelopmental disability; major medical disorders, including neurological disorders; and pregnancy. Interview and clinical assessments were performed during each patient’s first hospital visit. All self-report scales were administered to participants on the same day to minimize recall bias after medication commencement. Written informed consent was obtained from participants after the study’s methods and purpose of the study were explained to them. All study procedures adhered to the Institutional Review Board (IRB) regulations and the principles of Good Clinical Practice at CHA Bundang Medical Center (IRB no. 2022-10-041).

DUI and clinical assessments

DUI

DUI was defined as the time interval (in months) between the onset of psychiatric symptoms and the initiation of psychiatric intervention. The onset was determined as the time when psychiatric symptoms first fulfilled the DSM-5 diagnostic criteria for PD, whereas the initiation of intervention was marked by the first psychiatric consultation for diagnosis or pharmacotherapy at standard dosages for a sufficient duration [24,25]. Further, DUI was assessed by both patient self-report (e.g., When did you first experience anxiety symptoms, and how frequently did they occur?) and clinical interviews conducted by trained clinicians using the Structured Clinical Interview for DSM disorders; additionally, the interview data were corroborated by examining relevant clinical charts (e.g., date of first psychiatric consultation, history of previous psychiatry or emergency visits, and psychiatric medication prescription dates).

The Scale for Suicide Ideation (SSI), Panic Disorder Severity Scale (PDSS), and Beck Depression Inventory-II (BDI-II) were utilized to analyze SI and other clinical characteristics.

Suicidal ideation

Notably, SI—defined as thinking about, considering, or planning suicide—is a critical risk factor for suicide attempts and completed suicide [9]. The SSI is a clinician-administered rating scale that assesses the intensity of current conscious suicidal intent by measuring various dimensions of self-destructive thoughts. The SSI comprises 19 items, rated on a 3-point Likert scale ranging from 0 to 2 (total scores: 0–38) and classified based on suicidality severity. Additionally, the Korean version of the SSI employed in this study demonstrates strong internal consistency (α=0.74) [26]. Higher SSI total scores indicate higher suicide risk, and the “high risk” category refers to an SSI total score of 2 or more [27].

Depression

The Korean version of the BDI-II comprises 21 items evaluating the severity of depressive symptoms, which demonstrates high internal consistency (Cronbach’s α=0.85) [28]. Responses are rated on a scale ranging from 0 to 3 (total scores: 0–63).

Panic symptom severity

The PDSS is a self-report assessment of panic symptoms comprising 7 items regarding the frequency of panic attacks, anticipatory anxiety, phobic responses, the severity of panic symptoms, and dysfunction in work and social domains. The PDSS is based on a 5-point Likert scale ranging from 0 to 4 (total scores: 20–80) [29]. The Korean version of the PDSS, which exhibits strong internal consistency (Cronbach’s α=0.88) [30], was utilized.

Statistical analyses

Frequency analyses were performed to analyze sociodemographic and clinical characteristics. Group differences in SI according to categorical variables (e.g., gender, educational level, employment, income, and marital status) were examined using independent t-tests. Pearson’s correlation analyses were used to evaluate the relationships among continuous variables (e.g., SSI total scores, age, DUI, BDI-II total scores, and PDSS total scores). Multiple regression analysis was performed to identify independent factors of SSI among patients with PD. All statistical analyses were conducted using SPSS version 29.0 (IBM Corp.), with significance set at p<0.05 (two-tailed).

RESULTS

Sociodemographic and clinical characteristics

As Table 1 summarizes, the study sample included 804 patients with PD (382 men and 422 women), with a mean age of 38.48 years (SD=11.51). Approximately 60% had a college education or higher. Further, among the participants, 91.3% were employed, nearly 90% earned over $1,800 per month, and 62% were married and living with partners. The mean DUI was 41.56 months (SD=66.68). The mean total scores were 5.23 (SD=6.69) for the SSI, 15.86 (SD=11.42) for the BDI-II, and 10.54 (SD=6.34) for the PDSS.

Table 1.

Sociodemographic and clinical characteristics of study participants (N=804)

	Values
Sociodemographic
Age (yr)	38.48±11.51
Gender
Men	382 (47.5)
Women	422 (52.5)
Level of education
High school or less	322 (40.0)
College or more	482 (60.0)
Job status
Unemployment	70 (8.7)
Employment	734 (91.3)
Monthly income
Below 1,800 $USD	78 (9.7)
Above 1,800 $USD	726 (90.3)
Marital status
Living with partner	498 (61.9)
Living without partner	306 (38.1)
Clinical variables
DUI (months)	41.56±66.68
Panic disorder symptom severity (PDSS total score)	10.54±6.34
Depression severity (BDI-II total score)	15.86±11.42
Suicidal ideation (SSI total score)	5.23±6.69

Values represent number (%) or mean±standard deviation. DUI, duration of untreated illness; PDSS, Panic Disorder Severity Scale; BDI-II, Beck Depression Inventory-II; SSI, Scale for Suicide Ideation.

Association between SI and categorical variables among patients with PD

Independent t-tests revealed significant group differences in SSI scores (Table 2), which were significantly higher among women and those who had lower educational levels, were unemployed, had a monthly income below $1,800, and were unmarried and living without a partner.

Table 2.

Association between suicidal ideation (SSI) and categorical variables among patients with panic disorder

Categorical variables	Mean±SD	t	p
Gender		-2.914	0.004**
Men (N=382)	4.21±5.96
Women (N=422)	6.23±7.22
Level of education		-2.972	0.003**
High school or less (N=322)	6.80±7.32
College or more (N=482)	4.47±6.25
Job status		-2.430	0.021*
Unemployment (N=70)	8.63±8.14
Employment (N=734)	4.92±6.47
Monthly income		-2.988	0.003**
Below 1,800 $USD (N=78)	8.89±7.15
Above 1,800 $USD (N=726)	4.93±6.58
Marital status		-4.580	<0.001***
Living with partner (N=498)	3.81±5.67
Living without partner (N=306)	7.08±7.46

^*p<0.05;

^**p<0.01;

^***p<0.001.

SSI, Scale for Suicidal Ideation.

Pearson’s correlations among continuous variables among patients with PD

Table 3 presents the results of the correlation analysis between continuous variables. The total SSI scores revealed significant correlations with lower age, longer DUI, higher BDI-II total scores, and PDSS total scores. Moreover, DUI was correlated with age, exhibiting no significant relationships with BDI-II or PDSS total scores.

Table 3.

Pearson’s correlations among continuous variables among patients with panic disorder

Continuous variables	SSI	Age	DUI	BDI-II	PDSS
SSI	-
Age	-0.209***	-
DUI	0.137*	0.168***	-
BDI-II	0.632***	-0.189***	0.050	-
PDSS	0.359***	-0.224***	-0.007	0.517***	-

^*p<0.05;

^**p<0.01;

^***p<0.001.

SSI, Scale for Suicide Ideation; DUI, duration of untreated illness; BDI-II, Beck Depression Inventory-II; PDSS, Panic Disorder Severity Scale.

Multiple regression analyses predicting suicidal ideation risk among patients with PD

Table 4 presents the results of the multiple regression analyses performed to identify the model predicting SI among patients with PD. No multicollinearity and residual problems were found (variance inflation factor, <10; Durbin-Watson=2.007). The model fits well with significance in predicting SI (Adj R2=0.427, F=24.630, p<0.001). Among the clinical variables, DUI (B=0.116, p=0.012) significantly predicted SSI total scores. Additionally, depression (B=0.508, p<0.001) and sociodemographic variables, including being a woman (B=0.124, p=0.007) and living without a partner (B=0.143, p=0.011), were significantly associated with SSI total scores.

Table 4.

Multiple regression analyses predicting suicidal ideation risk among patients with panic disorder

	B	t	p
Sociodemographic variables
Age (yr)	-0.034	-0.600	0.549
Gender (women)	0.124	2.707	0.007**
Level of education (high school or less)	0.065	1.431	0.154
Job status (unemployment)	0.064	1.397	0.164
Monthly income (below 1,800 $USD)	0.021	0.458	0.647
Marital status (living without partner)	0.143	2.560	0.011*
Clinical variables
DUI (months)	0.116	2.524	0.012*
Depression severity (BDI-II)	0.508	9.756	<0.001***
Panic disorder symptom severity (PDSS)	0.071	1.375	0.170
Constant	-3.097
F	24.630 (<0.001***)
R2	0.445
Adj R2	0.427

Reference group: gender (men), education (college or more), job status (employment), monthly income (above 1,800 $), marital status (living with partner).

^*p<0.05;

^**p<0.01;

^***p<0.001.

DUI, duration of untreated illness; BDI-II, Beck Depression Inventory-II; PDSS, Panic Disorder Severity Scale.

DISCUSSION

To our knowledge, this is the first study to identify DUI as a potential risk factor for SI in a large clinical cohort of PD patients. Moreover, our prediction model demonstrated that being a woman and being unmarried as social determinants and severe depression as a clinical factor exerted significant effects on the elevated risk of SI.

Our analyses using independent t-tests and Pearson’s correlations suggested that several demographic factors—including age, educational levels, employment status, and monthly income—are associated with SI in PD. The relationship observed between younger age and increased SI aligned with prior findings [3], highlighting the impulsive–aggressive characteristics of younger suicides in the general population [31]. Individuals with lower educational levels exhibited higher suicide mortality rates and relied on ineffective coping strategies when dealing with stressful events [32]. Further, meta-analytic studies have reported that unemployed individuals are twice as likely to be involved in completed suicide as employed individuals [33] and that those with low income tend to exhibit increased suicidal behaviors [34].

Our findings highlighted a positive effect of prolonged DUI on suicidality among patients with PD. The average DUI among our participants (41.56 months) was similar to that reported in a previous research involving outpatients with PD (44.35±59.86 months) [35]. Additionally, we found that older age was positively correlated with longer DUI—supported by previous research showing that older individuals are less likely to seek or visit health providers, resulting in prolonged DUI and symptom persistence [36,37]. Our results align with prior studies demonstrating the relationship between longer DUI and increased suicidal attempts in both mood and anxiety disorders [35,38].

Prolonged DUI in PD may foster poor treatment outcomes, including recurrence, chronicity, and frequent comorbidity with MDD [14,20], necessitating intensified specialized care19 and potentially contributing to suicidality [21]. The relationship between DUI and SI in PD can be explained by anxiety sensitivity, the fear of anxiety-related sensations induced by distorted interpretation [39]. Clark’s cognitive model argues that patients with PD exhibit a cognitive bias to interpret their interoceptions as a sign of life-threatening or dangerous diseases [40,41], which increases their suicidality risk because of their excessive worry of losing self-control. A recent study—grounded in network analysis—identified the fear of cognitive dyscontrol as the most central symptom in a network of patients with PD with a history of suicidal attempts. Moreover, their results demonstrated that the fear of cognitive dyscontrol has a direct pathway to higher suicide risk through amplified hopelessness [2]. To predict comprehensively, prolonged DUI may demoralize patients’ efficacy to self-control through aggravated symptomatology, including frequent attacks and heightened anxiety sensitivity, and consequently contribute to suicide. From a biological perspective, a preliminary study reported that higher DUI may be associated with decreased gray matter volumes in the inferior parietal lobule in PD [42].

While PD itself is an independent risk factor for SI after controlling for the presence of comorbid MDD [11], our findings indicated that depressive symptoms strongly predicted SI in PD—consistent with previous studies [6,43]. In the PD cohort, MDD was the most common psychiatric comorbidity, reported by approximately 63% of participants [11]. This result is attributable to the fact that the PD and MDD share vulnerability factors, such as neuroticism [44] and childhood trauma [45].

Among social determinants, our regression results revealed that SI in PD may exhibit gender differences—consistent with a previous study suggesting that women patients with PD are more likely than men patients to engage in suicidal behaviors [46]. These gender differences in SI may be biologically explained by significant fluctuations in gonadal hormones, which affect the brain regions involved in affective and behavioral regulation among women [47]. Thus, women are more likely than men to be susceptible to affective disorders, including negative affectivity [48] and neuroticism [49]. Furthermore, women patients with PD are more likely than men patients to experience comorbidity with agoraphobia; recurrence after remission; and stressful life events, including separation, physical diseases, and pregnancy-related issues. Although multiple risk factors are associated with SI among women patients with PD, they rarely utilize effective coping strategies, such as confrontation and seeking social support, which may further aggravate SI [50].

Additionally, our study found that living alone significantly increased SI risk in PD. Previous studies have reported that patients with PD may have vulnerabilities to dependence, including separation anxiety [51], internalizing fear [39], and insecure anxious attachment [52]. Separation anxiety, the precursor of PD or agoraphobia [53], and insecure anxious attachment were highly correlated with suicidal behaviors among patients with PD [54]. Specifically, patients with PD with marital maladjustment exhibited extremely severe symptoms, such as catastrophic thoughts, interoceptive fear, and fear of repercussions of anxiety [55]. Supportive social relationships, including marriage, may encourage help-seeking behaviors and treatment adherence [56,57] and alleviate symptom severity [58] among patients with PD [59].

This study had several limitations. First, because DUI was measured retrospectively, recall bias should be considered—specifically, patient self-report errors, such as over- or underestimating their mental health symptoms. To minimize recall bias, psychiatric consultations were supplemented with chart reviews conducted by trained clinicians. Second, our results were limited to a clinical sample from three hospitals in South Korea, which necessitates caution when generalizing the findings. Thus, future large-scale epidemiological research must focus on generalizing the effects of DUI on SI in PD. Although studies targeting specific clinical samples may provide insights into developing effective intervention strategies by considering their specificity, epidemiological studies are crucial for identifying—through regular screening and monitoring—potential patients who exhibit symptoms but do not seek medical help. Third, this study’s cross-sectional design limits causal inference owing to unclear temporal relationships and potential unaccounted-for demographic or clinical confounding factors. Thus, future prospective cohort studies must aim to establish causality by exploring additional factors that may influence SI in PD.

As our data are derived from South Korean patients with PD, unique cultural characteristics may have influenced both DUI and suicidality. First, patterns of help-seeking behavior should be considered. In East Asian collectivist cultures, wherein high tolerance of “Chemyon” is regarded as a virtue, visiting mental health professionals may be perceived as a weakness and incompetence [60]. Specifically, individuals are culturally trained to suppress expressing their negative emotions [61] and may consequently underestimate the severity of their suicidal behaviors or delay seeking professional help [62]. Second, mental health stigma may contribute to a prolonged DUI. A survey conducted by the Korean National Mental Health Center in 2024 reported that approximately 65% of respondents had stigma that individuals with mental illness are more hazardous than those without [63]. Consistently, South Korean psychiatric patients suffered from the most severe social exclusion among all disability groups—at least 6–10 times higher [64,65]. This social exclusion may further lengthen DUI [66]. Stigma and discrimination against psychiatric patients, though particularly severe in South Korea, manifest as cross-cultural phenomena [67]. Heightened exposure to discrimination (e.g., social exclusion) is strongly associated with reduced problem-solving efforts and diminished control over life circumstances [68], both of which are positively correlated with suicidality [69,70]. These findings suggest that our results may be generalizable to other countries, pending further replication.

In conclusion, this study identified prolonged DUI as a robust predictor of increased suicidality in PD, even after controlling for sociodemographic and other clinical factors. Our findings suggest that reducing DUI may help prevent suicide attempts with mortality risk among patients with PD by alleviating their fear of losing control and mitigating severe symptoms. Additionally, our results comprehensively highlight key social determinants (i.e., being a woman and unmarried) and clinical factors (i.e., depression) that should be considered when screening for suicidality in PD. These findings underscore the importance of primary intervention in decreasing DUI and suicidality in PD. From a clinical perspective, our results may inform the development of screening programs for PD and suicidality in primary care and community settings, thus facilitating early detection and timely intervention. Additionally, digital mental health literacy initiatives involving mobile-based self-rating measurements and psychoeducation content may help reduce stigma, improve illness insight, and promote help-seeking behaviors. Systemically, collaborative care models that connect primary clinicians with mental health professionals, including psychiatrists, clinical psychologists, and social workers, could enable ongoing follow-up monitoring and integrative interventions. Collectively, these strategies could contribute to reducing DUI and mitigating suicide risk among patients with PD.