As Korea ranks first in suicide rates among OECD countries, the need for treatment support for ‘treatment-resistant depression’ is being emphasized.

Experts stress the need for alternatives in treating treatment-resistant depression, a condition known to have a sevenfold higher risk of suicide attempts compared to general depression.

On September 9, to mark World Suicide Prevention Day, Janssen Korea held a Masterclass to share the current state of TRD and the latest treatment insights.

According to Statistics Korea's ‘2023 Cause of Death Statistics’, 13,978 people died by suicide in 2023. The suicide rate per 100,000 people in 2023 was 27.3, an 8.5% increase compared to 2022. This ranks Korea first among OECD countries in suicide rates, exceeding the OECD average by more than double.

Depression is cited as one of the major factors for suicide. Psychological autopsy results from 1,099 suicide deaths over nine years from 2015 to 2023 (MOHW/Korea Foundation for Suicide Prevention, 2023 Psychological Autopsy Interview Results Report) estimated that 86.3% had suffered from mental illness prior to death, with 74.5% identified as having depressive disorder.

Among those suspected of having a mental illness, 60.5% had received treatment or counseling for mental health issues before their death.

Professor Sung-jun Cho of Kangbuk Samsung Hospital’s Department of Psychiatry noted, “In Korea, we can see that the prevalence of depression has surpassed the one million mark, which is significantly higher than in other countries. Because it is difficult to clearly define the presence or absence of depression, treatment is often challenging.”

Major depressive disorder refers to a condition where persistent depressive mood and loss of interest lasting at least two weeks are accompanied by multiple physical symptoms and significant impairment of daily functioning. Among these patients, about 1 in 3 may have TRD, showing no response to various antidepressant treatments.

TRD is generally defined as the ‘absence of a clinical response despite administration of at least two oral antidepressants at adequate doses for a sufficient duration.’

Professor Cho stated, “TRD patients incur over 40% more healthcare costs than patients with major depressive disorder. Not only is treatment difficult, but relapse rates are also higher compared to patients with major depressive disorder. Severe patients who struggle to maintain employment may experience a vicious cycle where their economic burden increases.”

However, there is currently no universally standardized treatment for TRD.

Treatment options for TRD include pharmacotherapy such as antidepressant optimization, switching or combination therapy, and augmentation therapy, as well as procedures like repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). However, conventional pharmacotherapy takes time to achieve remission, making it difficult to expect an immediate response to suicidal impulses.

Conventional depression treatments take approximately 37 to 51 days to achieve remission, making it easy to miss the golden window for treatment. Furthermore, the remission rate decreases sharply with each treatment failure.

Amidst the growing need for rapid and effective treatments for TRD, attention is turning to the role Spravato (esketamine hydrochloride) could play in the field.

It is the only drug approved in Korea for treatment-resistant depression. Unlike existing antidepressants targeting serotonin and norepinephrine, Spravato is a novel antidepressant acting on the NMDA receptor.

Clinical studies have shown that Spravato produced clinically significant symptom improvement within 24 hours in TRD patients, achieving a 52.5% remission rate after 28 days of treatment. Furthermore, patients who maintained remission after 16 weeks of Spravato treatment saw a 51% reduction in relapse risk when treatment was continued.

Professor Cho stated, “After about a month of Spravato treatment—once the induction phase was complete—more than half of the patients not only responded but reached remission. The rapid onset of effect, sometimes as early as the day after administration, is particularly notable.”

However, Spravato is known to cost approximately KRW 400,000 per administration as it is not covered by reimbursement.

Typically, two doses are administered per treatment session, costing about KRW 800,000 per visit. In the early stages, treatment is usually given twice per week, resulting in a weekly cost of about KRW 1.6 million. This high cost inevitably creates barriers to patient access.

Current domestic suicide prevention policies for high-risk groups are limited to supporting treatment costs for injuries resulting from suicide attempts, counseling, and case management for attempters and bereaved families.

Professor Cho argues that providing integrated healthcare services extending to practical treatments that can lead to long-term suicide prevention is necessary.

Professor Cho stated, “In the clinical setting, there is talk that Spravato could realistically contribute to lowering suicide rates. However, there inevitably exists a cost barrier preventing its actual prescription.”

He added, “We are beginning to see changes, such as the Jeonbuk Mental Health Welfare Center’s support program covering Spravato treatment costs for major depressive disorder patients. We need more initiatives like this to ensure continuous, active treatment.