Clinical Efficacy of Chaihu Jia Longgu Muli Decoction Combined with Cognitive Behavioral Therapy for Insomnia in the Treatment of Acute Insomnia with Liver Depression Transforming into Fire Pattern

Abstract

Objective: To evaluate the clinical efficacy of Chaihu Jia Longgu Muli Decoction combined with Cognitive Behavioral Therapy for Insomnia (CBT-I) in treating patients with acute insomnia characterized by the "Liver Depression Transforming into Fire" pattern.

Methods: A randomized controlled trial was conducted involving 90 patients meeting the diagnostic criteria for acute insomnia and the Traditional Chinese Medicine (TCM) pattern of Liver Depression Transforming into Fire. Participants were randomly assigned to either the observation group ($n=45$) or the control group ($n=45$). The control group received standard CBT-I, while the observation group received a combination of CBT-I and Chaihu Jia Longgu Muli Decoction. The primary outcome measures included the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and TCM syndrome scores. Secondary outcomes included sleep parameters recorded via photoplethysmography (PPG) and serum levels of TNF-$\alpha$, IL-$1\beta$, and 5-HT.

Results: After the 4-week intervention, the total effective rate in the observation group was 88.89%, significantly higher than the 66.67% in the control group ($P < 0.05$). Both groups showed significant improvements in PSQI, HAMA, and HAMD scores compared to baseline ($P < 0.05$). However, the observation group demonstrated significantly greater improvements in sleep latency, total sleep time, and TCM syndrome scores compared to the control group ($P < 0.05$). Furthermore, the observation group showed significantly lower levels of inflammatory factors (TNF-$\alpha$, IL-$1\beta$) and higher levels of 5-HT ($P < 0.05$). No serious adverse events were reported.

Conclusion: The combination of Chaihu Jia Longgu Muli Decoction and CBT-I is more effective than CBT-I alone for treating acute insomnia with the Liver Depression Transforming into Fire pattern. This integrated approach improves sleep quality, alleviates emotional distress, and regulates relevant biomarkers.

1 Introduction

Acute insomnia is a sleep disorder characterized by frequent episodes (more than three times per week) and a short duration (less than three months). Epidemiological surveys indicate that its global prevalence is as high as 30% to 50%. While symptoms sometimes resolve spontaneously once triggers are removed, recent clinical evidence demonstrates that acute insomnia carries a high risk of recurrence and a significant tendency to transition into chronic insomnia, making it a critical window for intervention. Currently, clinical treatment primarily relies on benzodiazepine sedatives; however, long-term use may lead to adverse effects, including drug dependency and cognitive impairment \cite{4}.

Although cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first-line non-pharmacological treatment, clinical practice has shown that its efficacy as a monotherapy can be limited by patient compliance. Within Traditional Chinese Medicine (TCM) theory, the "Liver Depression Transforming into Fire" pattern is a prevalent phenotype of insomnia. Typical symptoms include difficulty falling asleep, irritability, chest tightness, a red tongue with a yellow coating, and a wiry, rapid pulse. Chaihu Jia Longgu Muli Decoction, a classic formula from the Shanghan Lun, is recognized for its ability to harmonize the Shao-yang and tranquilize the mind. This study aims to evaluate the efficacy of combining this formula with CBT-I.

2 Methods

2.1 General Data

A total of 90 patients diagnosed with acute insomnia of the liver-stagnation transforming into fire type at the 901st Hospital of the Joint Logistic Support Force between March 2023 and September 2024 were prospectively enrolled. Participants were divided into a control group and an observation group ($n=45$ each) using a random number table. The study was approved by the Medical Ethics Committee (No. 202107001). Inclusion criteria included age 18–65, PSQI $> 7$, and disease duration $< 3$ months. Exclusion criteria included severe psychiatric disorders (HAMA $\ge 29$ or HAMD $\ge 24$), organ failure, or pregnancy.

2.2 Therapeutic Interventions

The control group received CBT-I, including sleep hygiene education, stimulus control therapy, sleep restriction therapy, relaxation training, and cognitive therapy. The observation group received CBT-I plus Chaihu Jia Longgu Muli Decoction. The herbal composition included: Radix Bupleuri (Chaihu) 12g, Radix Scutellariae (Huangqin) 9g, Rhizoma Zingiberis Recens (Shengjiang) 9g, Radix Ginseng (Renshen) 9g, Concha Margaritifera (Zhenzhumu) 30g, Poria (Fuling) 12g, Ramulus Cinnamomi (Guizhi) 9g, and calcined Os Draconis and Concha Ostreae (Duan Longmu) 30g each. The decoction was administered twice daily for 4 weeks.

2.3 Evaluation Indices

1. Clinical Efficacy: Categorized as recovered, markedly effective, effective, or ineffective based on PSQI reduction.
2. Objective Sleep Quality: Monitored via photoplethysmography (PPG) for total sleep time, sleep latency, and sleep efficiency.
3. Scale Assessments: PSQI, HAMA, HAMD, and TCM syndrome scores.
4. Serum Biomarkers: TNF-$\alpha$, IL-$1\beta$, and 5-HT measured via ELISA.

3 Results

3.1 Clinical Efficacy

The total effective rate in the observation group (88.89%) was significantly higher than in the control group (66.67%, $P < 0.05$).

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3.2 Sleep Parameters and Scale Scores

Post-treatment, the observation group exhibited significantly higher total sleep time and sleep efficiency, and significantly lower sleep latency and fewer awakenings compared to the control group ($P < 0.05$). PSQI, HAMA, and HAMD scores in the observation group were also significantly lower than those in the control group ($P < 0.05$).

[TABLE:3]
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3.3 TCM Syndrome Scores and Biomarkers

Post-treatment TCM syndrome scores in the observation group were significantly lower than in the control group ($P < 0.05$). Furthermore, the observation group showed significantly lower levels of TNF-$\alpha$ and IL-$1\beta$, and significantly higher levels of 5-HT compared to the control group ($P < 0.05$).

[TABLE:5]

3.4 Safety

One case of dizziness and one case of nausea were reported in the observation group (4.44%). There was no statistically significant difference in the incidence of adverse reactions between the two groups ($P > 0.05$).

4 Discussion

Acute insomnia often progresses to chronic illness if not treated effectively during the early stages. While CBT-I is the gold standard for non-pharmacological treatment, its efficacy is often hindered by low patient compliance. This study demonstrates that the addition of Chaihu Jia Longgu Muli Decoction significantly enhances therapeutic outcomes.

From a TCM perspective, the "Liver Depression Transforming into Fire" pattern involves emotional stagnation leading to internal heat that disturbs the Shen (spirit). The formula used in this study harmonizes the Shao-yang, clears heat, and heavily sedates the mind using minerals like Os Draconis and Concha Ostreae. Our results show that this combination not only improves subjective sleep quality (PSQI) but also objective parameters (PPG) and emotional states (HAMA/HAMD).

The physiological mechanism may be related to the regulation of inflammatory cytokines and neurotransmitters. Elevated levels of TNF-$\alpha$ and IL-$1\beta$ are associated with sleep disruption, while 5-HT is a key promoter of slow-wave sleep. The observation group showed a more significant reduction in inflammatory markers and an increase in 5-HT, suggesting that the herbal formula works synergistically with behavioral therapy to restore neuroendocrine balance.

In conclusion, the combination of Chaihu Jia Longgu Muli Decoction and CBT-I is a safe and effective strategy for managing acute insomnia of the liver depression transforming into fire type, offering superior results in sleep restoration and emotional stabilization compared to monotherapy.