Treatment of Tension-type Headache by Zhixuan Analgesic Tablets

Background and Rationale:

Tension-type headache (TTH) is the most common primary headache disorder worldwide. In its frequent episodic form, headaches occur on 4 to 14 days per month, and although individual attacks are usually of mild-to-moderate intensity, the high frequency of episodes imposes a substantial cumulative burden: impaired daily functioning, reduced work productivity, diminished quality of life, and escalating reliance on acute pain medications, which in turn increases the risk of medication-overuse headache. Evidence-based prophylactic options remain limited, and many patients turn to traditional Chinese medicine (TCM). However, the efficacy and safety of many TCM preparations for headache have not yet been rigorously evaluated in controlled trials.

Zhixuan Analgesic Tablet is a TCM preparation intended for headache management. Its use in this trial is guided by TCM syndrome differentiation, targeting patients whose headache is primarily attributed to Liver-Yang Ascending Syndrome and/or Static Blood Obstructing the Collaterals Syndrome - patterns frequently implicated in tension-type headache. This study seeks to generate high-quality, controlled evidence on whether Zhixuan Analgesic Tablet can reduce the frequency and burden of headache attacks and improve patients' daily functioning, while establishing its safety profile.

Study Design and Procedures:

This is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group trial involving 212 participants, conducted from December 2025 through December 2026.

Eligible participants will first enter a 4-week screening/baseline period, during which they document their headaches in a daily diary to confirm eligibility and establish baseline headache burden. Those confirmed eligible will then be randomly assigned to receive either Zhixuan Analgesic Tablet (4 tablets, three times daily) or a matching placebo for a treatment period of 12 weeks. All study medication is identical in appearance, and neither participants nor study staff will be aware of treatment allocation throughout the trial.

During the treatment period, participants will continue to maintain the daily headache diary, recording the occurrence, duration, and intensity of each headache episode, as well as any use of acute analgesic (rescue) medication. Participants will attend scheduled clinic visits for clinical evaluation, review of diary data, assessment of treatment compliance, and monitoring of adverse events. At the conclusion of treatment, participants will complete the Headache Impact Test (HIT-6) - a validated instrument quantifying the impact of headache on daily life - and provide a global self-assessment of treatment effectiveness.

Outcomes and Safety:

The primary outcome is the number of headache days within each 4-week interval during the treatment period. Secondary outcomes address the use of acute analgesic medication, the total duration of moderate-to-severe headache, average and peak headache intensity, the impact of headache on daily life, participants' global assessment, and the proportion of participants achieving at least a 30% reduction in headache days.

Safety is monitored throughout the trial through the collection of adverse events - including allergic and gastrointestinal reactions - elicited via open-ended questioning at each study visit. The incidence of adverse events and any resulting discontinuation of the study drug are recorded and analyzed.

Significance:

By applying rigorous methodology - randomization, blinding, placebo control, and validated outcome measures - to a TCM intervention, this trial aims to provide reliable evidence to support clinical decision-making and ultimately to offer patients with frequent episodic tension-type headache a safe, effective, and well-characterized additional treatment option.