'Insomnia can become chronic if left untreated'

Limited use of cognitive behavioral therapy in Korea…entrenched reliance on pharmacotherapy

Tolerance and dependence limitations of sleep medications…need for new treatment options rise

The importance of timely treatment of insomnia is being emphasized, as insomnia, once considered merely a lack of sleep, can develop into a chronic condition if it persists.

While the number of patients diagnosed and treated in Korea remains at around 700,000, it is estimated that 20–30% of adults actually experience insomnia symptoms. As the gap between symptom experience and treatment persists, the need for early intervention is increasing.

Professor Wonju Kim of the Department of Neurology at Gangnam Severance Hospital explained in a recent interview with Daily Pharm, “Insomnia does not simply mean having difficulty falling asleep. It is a disorder that also includes repeatedly waking up during sleep or waking up earlier than planned. We consider treatment necessary when these sleep problems persist and lead to impaired daily functioning, such as fatigue, decreased concentration, and daytime sleepiness.”

He continued, “If appropriate intervention is not made, especially in the early stages, symptoms can become prolonged and progress into chronic insomnia. It is crucial not to miss the optimal timing for treatment.”

Lack of sleep increases the risk of systemic diseases… the importance of insomnia management highlighted

Professor Wonju Kim, Department of Neurology, Gangnam Severance Hospital

Insomnia manifests in various forms, including ▲ difficulty falling asleep, ▲ difficulty staying asleep, and ▲ waking up too early in the morning. It is classified as a medical condition, not merely a lack of sleep, but when it is accompanied by a decline in daily functioning.

In particular, acute insomnia caused temporarily by external stress can progress to chronic insomnia lasting more than three months if left untreated.

Professor Kim said, “The longer insomnia persists, the more difficult it becomes to treat, and the longer treatment may take. Active treatment in the early stage is important.”

According to the HIRA Open Data Portal, the number of patients with insomnia in Korea increased from about 650,000 in 2020 to about 760,000 in 2024.

Insomnia affects not only sleep but also overall health. Persistent sleep deprivation is known to be associated with reduced concentration, emotional dysregulation, as well as increased risks of cardiovascular disease, diabetes, and depression.

Currently, insomnia treatment is divided into cognitive behavioral therapy and pharmacotherapy. Although cognitive behavioral therapy is recommended as the standard treatment, its use is limited in Korea, resulting in a treatment structure that relies heavily on medication in actual clinical practice.

Professor Kim explained, “Cognitive behavioral therapy involves identifying a patient’s sleep habits, analyzing them, and continuously correcting inappropriate sleep behaviors. It also includes correcting the misconception that insomnia is an extremely severe disease. However, in Korea, such treatment is not widely implemented due to high manpower requirements and constraints such as insurance reimbursement.”

New alternatives amid limitations of pharmacotherapy…DORA proposes an approach based on regulating the arousal system

Pharmacotherapy typically includes benzodiazepines and non-benzodiazepine agents, as well as other drugs acting on the same receptors, melatonin, antihistamines, and antidepressants.

Professor Kim said, “Existing drugs have proven efficacy, but there is a burden associated with long-term use due to tolerance and dependence issues. Both patients and healthcare providers often face difficulties in maintaining treatment.”

He continued, “There is also the issue where efficacy gradually decreases with long-term use, leading to the need to increase the dosage. In elderly patients, there have been reports of the drug’s effects persisting into the next day or abnormal behaviors such as nightmares and sleepwalking. Such side effects are particularly prominent with zolpidem-class drugs.”

Amid these limitations, a new treatment approach that regulates the arousal system, DORA (dual orexin receptor antagonist) class drugs, is gaining attention.

DORA works by binding to and inhibiting orexin receptors (OX1R, OX2R), which are neurotransmitters responsible for maintaining wakefulness, thereby lowering arousal levels and inducing sleep. This is a fundamentally different approach from conventional methods that directly suppress the central nervous system to induce drowsiness.

Professor Kim stated, “Unlike melatonin, which induces sleep, orexin is a neurotransmitter that maintains wakefulness. Sleep and wakefulness exist in a balanced relationship. When wakefulness increases, sleep decreases, and conversely, when sleep increases, wakefulness decreases.”

Orexin is produced and secreted by neurons and plays an important role in maintaining wakefulness. A deficiency of this substance is associated with narcolepsy, a condition characterized by an inability to maintain wakefulness and sudden episodes of falling asleep, which is known to be associated with reduced orexin secretion.

DORA utilizes this mechanism in reverse. It works by blocking orexin receptors to reduce excessive wakefulness, thereby inducing more natural sleep.

This approach differs from existing benzodiazepine-class drugs in that it does not simply induce drowsiness but regulates the sleep-wake balance itself. In particular, while GABA-class sleep aids such as zolpidem affect sleep architecture, including slow-wave sleep and REM sleep, DORA is gaining attention for its ability to induce more physiological sleep without significantly disrupting sleep structure.

Professor Kim stated, “DORA-class drugs lower arousal levels to induce more natural sleep. Another characteristic is that they do not significantly alter sleep structure. They hold the potential to alleviate the concerns of tolerance and dependence that have been problematic in existing treatments, and are meaningful in expanding the range of insomnia treatment strategies.”

However, the most important factors in treating insomnia remain lifestyle adjustments and environmental modifications.

Professor Kim added, “Insomnia often arises from a combination of lifestyle habits and psychological factors. Approaches that correct sleep habits must be combined with drug therapy. Above all, it is crucial for patients to recognize insomnia as a medical condition and begin treatment early. Not missing the treatment window determines long-term prognosis.”