Desvenlafaxine for Preventive Treatment of Frequent Episodic Tension-type Headache

This randomized, double-blind, placebo-controlled trial aims to assess the efficacy of Desvenlafaxine (a serotonin-norepinephrine reuptake inhibitor) in reducing the frequency and severity of tension-type headache (TTH) attacks in adult patients with episodic TTH.

• Desvenlafaxine (Drug): Desvenlafaxine
• Placebo (Drug): Placebo

Primary outcomes

• Days with tension-type headache (TTH) during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12) [During the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)]: Days with tension-type headache (TTH) during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)

Secondary outcomes

• Total headache index AUC (area under the curve) during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12) [during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)]: Total headache index AUC (area under the curve) during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)
• Headache severity (VAS 0-10) and duration (hours per day) during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12) [during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)]: Headache severity (VAS 0-10) and duration (hours per day) during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)
• Acute analgesic consumption: number of days and dosage [during the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)]: Acute analgesic consumption: number of days and dosage
• Treatment effectiveness criterion: reduction in headache days by ≥50% during the third 4-week intervention period compared to the screening period [during the third 4-week intervention period]: Treatment effectiveness criterion: reduction in headache days by ≥50% during the third 4-week intervention period compared to the screening period
• Safety assessment and tolerability evaluation [During the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)]: Safety and tolerability will be evaluated by: Continuous recording of treatment-emergent adverse events (TEAEs, graded by CTCAE v5.0) throughout the study.
• Change in headache impact on daily life as assessed by the 6-item Headache Impact Test (HIT-6) total score [During the 12-week intervention period (reported in 4-week intervals: Weeks 0-4, 5-8, and 9-12)]: The HIT-6 questionnaire measures the adverse impact of headache on daily functioning in six domains (pain, social functioning, role functioning, vitality, cognitive functioning, psychological distress).

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

1. Male or female subjects aged 18-65 years
2. Meeting the diagnostic criteria for tension-type headache (TTH) according to ICHD-3; with ≥6 but <15 attack days per month in the past 3 months and MIDAS score >21; onset of TTH before age 50, with a history exceeding 1 year
3. Informed consent obtained from the patient

Exclusion Criteria:

1. History of allergy to Desvenlafaxine, or use of Desvenlafaxine within 4 weeks prior to the start of the treatment period; currently taking or requiring concomitant administration of drugs contraindicated in the package insert, such as monoamine oxidase inhibitors (MAOIs);
2. Diagnosable with chronic tension-type headache or medication overuse headache;
3. Comorbid with other types of headaches, such as trigeminal autonomic cephalalgias, migraine attacks >1 time/month within 3 months, or secondary headaches (e.g., those caused by intracranial infections, craniocerebral trauma, cerebrovascular diseases);
4. Severe psychiatric disorders such as schizophrenia, moderate to severe anxiety-depression (Hamilton scale ≥12 points); poorly controlled epilepsy, cognitive impairments, and other chronic pain conditions; serious organic diseases that pose significant health risks, including uncontrolled hypertension, cardiac disease, hepatic dysfunction, renal insufficiency, infections; any medical condition or prior surgery likely to affect the absorption, metabolism, or excretion of the study drug;
5. Concomitant use of venlafaxine analogues such as serotonin-norepinephrine reuptake inhibitors (SNRIs); unstable use of other preventive medications for TTH, including amitriptyline, mirtazapine (≤3 months); discontinuation of currently reported effective prophylactic drugs or overused analgesics for ≥3 months may allow re-enrollment;
6. Alcohol dependence or substance abuse;
7. Inability to comprehend the study protocol due to low education level, impaired verbal/language function, visual or auditory deficits; failure to accurately complete research materials like headache diaries or cooperate with scale assessments;
8. Women who are planning pregnancy, pregnant, breastfeeding, or not using contraception;
9. Participation in other interventional clinical studies that may influence outcome evaluations.

• Wensheng Qu, Principal investigator, Tongji Hospital