Electroconvulsive therapy for adolescents with severe depressive episode and suicidality: retrospective comparison between responders and non-responders

Adolescents around the globe are increasingly at risk of major depression, with the current two diagnostic standards providing specific definitions (major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, severe depressive episode in the International Classification of Diseases). What is clear is that major depression can significantly disrupt their lives and impede social functioning. Alarmingly, the global prevalence may reach up to 8% [1], with the possibility of even higher rates among American adolescents [2]. In China, which boasts a larger population, the estimated prevalence stands at 2% [3]—a figure that still represents a considerable number. Currently, depressive disorders have risen to rank as the fourth leading cause of the global burden of disease [4].

As major depression has become more pervasive, the risk of suicide has correspondingly increased, posing a grave threat to life and health [5]. Notably, suicide ranks as the leading cause of death among teenagers [6]. Consequently, psychiatrists are intensively working to develop rapid and effective treatments for depressive patients exhibiting suicidality.

ECT is the major treatment approach for adult depressive disorders with acute suicidal tendencies. This method is capable of significantly reducing both symptoms of depression and the risk of suicide [7], and its use among teenagers has been consistently growing. Recent retrospective research from various countries has shown that the response rates to ECT for adolescent major depression range from 72 to 78.6% [8‐11]. However, approximately one-third of patients fail to respond to this therapy. It is unclear what factors influence the clinical response to this therapy [9, 12].

In reviewing previous research on factors that influence adult ECT outcomes, older age has been identified as a demographic factor positively affecting treatment success [13]. Concurrently, factors such as accompanying psychotic symptoms [13], extended periods of depression, baseline medical treatment failure [14], suicidal ideation [15], and co-existing personality disorders [16] may be disease factor linked to treatment effectiveness. Regarding medical treatment aspects, medications that lower the threshold for seizures or shorten their duration can reduce ECT’s effectiveness [17]. Consequently, benzodiazepines (BDZs) and antiepileptic drugs are often considered the main factors affecting ECT's outcomes [18], with a general consensus to discontinue these medicines before therapy to prevent any impact on efficacy [19].

Research on adolescents is notably scarce, and the few existing studies indicate that among patients with depression undergoing ECT, features accompanying psychotic symptoms are correlated with higher relief rates [20]. Additionally, female major depressive cases with nonsuicidal self-injury (NSSI) [21], as well as those with fewer ECT sessions [11], may correlate with unsatisfactory outcomes, but many more contributing factors await clarification.

Recently, the First Affiliated Hospital of Chongqing Medical University (CQMU) has amassed a significant number of adolescent ECT cases. We intend to conduct a retrospective analysis on the ECT of depressive disorders with suicidal tendencies in teenagers, aiming to identify differences between successful and unsuccessful cases, thereby providing support for prognosis assessment and therapeutic guidance. We collected data on personal history, medical history, and standard treatment features to establish variables related to demographics, medical conditions, medications, and ECT treatment factors. Based on previous research, it is hypothesized that variables such as gender, disease duration, psychotic symptoms, suicidal behaviors, medication dosages, and ECT sessions may influence treatment effectiveness.

This study is a retrospective comparative research effort in which all patient names have been anonymized. Since the anonymized data cannot reveal the identity information of the patients, informed consent is not required. The Human Research and Ethics Committee of CQMU had approved this study (NO: 2022-K525).

In this study, 494 adolescent patients with severe depressive episode and suicidal behavior underwent ECT treatment; 361 (73.1%) of them responded effectively. The distribution of the CGI-I score can be found in Fig. 2.

In this retrospective clinical study, conducted over the past 5 years at the Department of Psychiatry in CQMU, an exhaustive analysis was performed on adolescents with severe depressive episode and suicidal tendencies who underwent ECT. The research utilized a substantial dataset to distinguish between effective and ineffective treatment outcomes. Consistent results were noted across various statistical models, and the reliability of these findings was substantiated through targeted subgroup analysis. This comprehensive examination encompassed non-responder characteristics, including demographic information, specific disease characteristics, medication interventions, and ECT treatment outcomes.

Within the scope of demographic variables, despite the narrow 7-year age range in the sample (11 to 18 years), a significant impact of age on treatment effectiveness emerged. This finding is in line with the consistent trend observed in prior meta-analyses [13], suggesting that the risk of ECT inefficacy decreases with age. Adolescence represents a crucial brain development phase characterized by dynamic alterations in brain structure and functionality [27]. A possible explanation for the varying ECT responses across different age groups could be the linear relationship between age and the degree of brain maturation. Yet, current scientific literature has not identified distinct brain differences in adolescents with depression across varying age groups [28]. As a result, some scholars argue that age might act as an intermediary factor connected with specific predictive symptoms, rather than directly impacting treatment effectiveness [29]. Further, other age-related aspects, such as advancing school grades creating unique environmental stressors, evolving and stable personality characteristics, increased social engagement, tendencies toward substance use, and greater access to online information, may all serve as mediators between age and treatment success.

Concerning disease variables, the study found that the presence of comorbid OCD significantly increases the risk of ECT treatment ineffectiveness compared to those without any comorbidities. Furthermore, we then compared the variables between the two ineffective patients and the three effective patients, and no statistically significant difference was observed. These findings align with outcomes from other studies on ECT treatment for bipolar depression [30] and mania [31], which similarly reported diminished efficacy in patients suffering from depression with comorbid OCD. The exact cause for this phenomenon remains unclear.

In investigating medication treatment factors, the study found notable differences among various medication. Specifically, when compared to sertraline, escitalopram was associated with an increased risk of ECT ineffectiveness. Conversely, olanzapine and aripiprazole were found to reduce the risk of ineffectiveness compared to quetiapine. These findings contrast with previous meta-analyses concerning medication treatments for adolescents. Two primary divergences were noted: (1) Previous studies have recommended escitalopram for treating major depressive disorder without an associated suicide risk [32]; (2) The efficacy of atypical antipsychotics (AAPs) in augmenting treatment-resistant depression appeared similar across different types, inconsistent with our findings [33]. It’s essential to recognize that our medication data were obtained at the time of discharge, necessitating a careful interpretation of the results. Upon examining the data, we identified a subset of patients on escitalopram who had previously exhibited a poor response to sertraline. This prior non-responsiveness could have influenced our results. However, the reported findings specifically center on escitalopram, potentially constraining a more holistic understanding of the medication-related outcomes. Furthermore, our research noted the inclusion of mood stabilizers in the discharge prescriptions, which could be intended for managing suicidal ideation, treatment-resistant depression, and significant irritability. It is important to highlight that while antiepileptic mood stabilizers are not recognized for their efficacy in alleviating suicidal tendencies [34], lithium salts may offer such benefits [35, 36]. This distinction draws attention to the need for more extensive research to verify the therapeutic potential of lithium in these contexts.

In the study’s examination of variables related to ECT treatment, a consistent pattern emerged: the risk of treatment ineffectiveness declined with 8 to 16 ECT sessions, a finding reinforced across different models and corroborated by subgroup analysis. This consistent reduction in risk was particularly stable within the 8 to 12 session range. Though other retrospective studies conducted in different regions of China did not provide the overall average ECT sessions for direct comparison between effective and ineffective groups, they did observe similar disparities (e.g., the effective group averaged 7.4 sessions versus an ineffective group averaged 6.6 sessions, P = 0.046) [11]. An Israeli retrospective study further emphasized this pattern, revealing that a significant number of patients only responded to treatment after more than 12 ECT sessions [12]. The finding underscores the importance of an adequately extensive ECT regimen to circumvent potential false-negative outcomes [12]. From the conducted research, it is revealed that the effective range of electroconvulsive therapy sessions for adolescents with severe depressive episode exceeds the AACAP's recommended range of 10–12 sessions [37]. This insight stresses the need for ongoing assessment of treatment response in adolescent patients in clinical practice, as it enables the development of personalized treatment plans. It's worth noting, however, that ECT treatments involving fewer than 8 sessions might not produce satisfactory therapeutic outcomes.

In this retrospective comparative study, we discovered that the risk of ineffective ECT in treating adolescent severe depressive episode with suicidal tendencies diminishes with increasing age. Furthermore, comorbidity with OCD notably elevates the risk of treatment failure, and administering fewer than 8 ECT sessions may hinder the achievement of satisfactory outcomes.