Acupuncture and Escitalopram for Treating Major Depression Clinical Study

This is a multicenter, randomized, controlled, 2 by 2 factorial clinical trial for Major depression.

• acupuncture (Other), also known as active acupuncture: The acupuncture group will receive treatment with needles inserted at the specified acupoints. Selected by acupuncture experts, these acupoints include DU20（Baihui) and SP4 (Gongsun) , PC6 (Neiguan) , PC5 (Jianshi) and LV 3 (Taichong) bilaterally. All acupoints are localized according to the WHO Standard Acupuncture Locations.After needle insertion, the acupuncture needles will be manipulated using either the twirling-rotating or lifting-thrusting methods to achieve the "De Qi" sensation.
• escitalopram (Other): Patients will receive 10 mg/day of escitalopram for the first 3 weeks and 20mg/day for the remaining 7 weeks.
• sham-acupuncure (Other): In the sham acupuncture group, superficial skin penetration (2 mm in depth) at nonacupoints will be done without De Qi manipulations. Nonacupoints are away from conventional acupoints or meridians. The choice of sham acupuncture points, which are points located in an emplacement different than the meridian points. The sham acupoints are not standard acupoints and will be about 1cun ( ≈20 mm) lateral from the real acupoints in the experimental group.
• escitalopram placebo (Other): Patients will receive 10 mg/day of escitalopram placebo for the first 3 weeks and 20mg/day for the remaining 7 weeks.

Primary outcomes

• HDRS-17 scale [from baseline to 10 weeks]: the change in the HDRS-17 score

Secondary outcomes

• Beck depression inventory scale [from baseline to 10 weeks]: the change in the Beck depression inventory score
• The CGI(Clinical Global Impression) scale [from baseline to 10 weeks]: the change in the CGI
• The GAD-7(General Anxiety Disorder) scale [from baseline to 10 weeks]: the change in the GAD-7
• The Mini-Mental State Examination (MMSE) scale [from baseline to 10 weeks]: the change in the MMSE

Other outcomes

• BDNF [at baseline and 10 week]: serum BDNF level
• IL18/IL-1β [at baseline and 10 week]: serum IL18/IL-1β level
• fMRI [at baseline and 10 week]: functional MRI

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Between 18 and 75 years of age with no gender-based restriction.
2. Fulfilling the diagnostic criteria of DSM-5 for major depressive disorder.
3. A Hamilton Rating Scale for Depression (HDRS-17) score ≥ 17
4. Ability to read and understand Mandarin Chinese, at least nine years of education, and willingness to adhere to the study protocol.
5. The absence of acupuncture treatment within at least 1 year.
6. Willingness to participate in the trial and provide written informed consent for the clinical trial.

Exclusion Criteria:

1. Lifetime or current neuropsychiatric conditions, such as bipolar disorder, schizophrenia, substance dependence or abuse, dementia, brain injury, epilepsy and so forth.
2. High suicide risk or presenting with suicidal ideation (a score of more than 2 points on the Suicide question of the HDRS-17) at the time of entry.
3. Medicated with antidepressant at the start of the trial or history of treatment failure to escitalopram.
4. Pregnancy or breastfeeding.
5. Subjects who have acute inflammation at the planned acupuncture site on the body or any other contraindication to acupuncture.
6. Candidates afraid of needles in general and reluctant to receive acupuncture in particular
7. Known or suspected clinically unstable systemic medical disorder (including cancer, organ failure, or severe diseases of the cardiovascular, severe hepatic or renal insufficiency).
8. Previous participation in other acupuncture trials.

• Results publication: Yang K, Tiwari S, Liu D, Xu Q, Qi L, Zhu Y, Jiang L, Zouqin H, Wong J, Chen J, Han Z. Acupuncture and Escitalopram for Treating Major Depression Clinical Study (AE-TMDCS): protocol for a factorial randomised controlled trial. BMJ Open. 2024 Sep 10;14(9):e091214. doi: 10.1136/bmjopen-2024-091214. PMID 39260834

• Zhenxiang Han, Dr, Principal investigator, Shanghai Seventh People's Hospital, Shanghai University of TCM