Can Acupuncture Treat Post-stroke Depression?

Stroke Clinical Trial

— PSD2  

Official title:

A Multisite, Assessor-blinded, Randomized Controlled Trial of Acupuncture for Post-stroke Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02644161
• Other study ID #: UW 15-421
• Status: Completed
• Phase: N/A
• Start date: October 2015
• Est. completion date: October 2018

Study information

• Verified date: May 2019
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An 8-week, assessor-blind, randomized controlled trial will be conducted. A total of 138 patients with post-stroke depression (PSD) will be randomly assigned to the combination acupuncture treatment (CAI) (n = 69) or least acupuncture stimulation (LAS) (n = 69) for 3 sessions per week for 8 weeks. Treatment outcomes will be measured using the 17-item Hamilton Self-Rating Depression Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), and Self-Rating Depression Scale (SDS) for depression symptoms; Barthel Index (BI) for physical function, the Montreal Cognitive Assessment (MoCA) for cognitive performance. The assessment will be performed at baseline and once monthly thereafter. The study will be conducted in School of Chinese Medicine Clinics, Tung Wah Hospital, Kowloon Hospital.

Description:

Mood depression is a common and serious consequence of stroke (Paolucci, 2008). There are approximately 30% of stroke patients developing PSD, either in the early or in the late stages after stroke (Paolucci, 2008). Despite the fact that PSD is strongly associated with the poor prognosis and an increased disability, it is often neglected in the clinical management, with only a minority of PSD patients who could receive proper diagnoses and treatment (Gustafson et al., 1995; Paolucci, 2008; Williams et al., 2004). Although pharmacological treatment, represented by various types of antidepressants, are recommended as first-line drugs for PSD, the effectiveness is unsatisfactory and the clinical use is largely hampered due to apparent shortcomings. A large portion of PSD patients could not obtain satisfactory outcomes from antidepressant treatment, in particular the elderly (Bhogal et al., 2005;Paolucci, 2008). Pharmacotherapy related side effects; particularly on cardiovascular system may exacerbate stroke patients' conditions (Paolucci, 2008). Furthermore, stroke patients are often medicated with various classes of drugs, the addition of antidepressant agents may increase risk of drug-drug interactions, resulting in unexpected and unpredictable adverse events (Hemeryck and Belpaire, 2002). The development of alternative treatment strategies for PSD patients is therefore highly desired.

While acupuncture is effective in reducing pain disorders, it also possesses psychotropic potential in treating psychiatric symptoms, in particular depression, anxiety and sleep disturbance. Our systematic review with meta-analysis suggests that the clinical outcomes of acupuncture is equivalent to antidepressant in treating major depression and superior to pharmacotherapy in improving clinical response and reducing the severity of PSD, with fewer incidences of adverse events (Zhang et al., 2010). Recently, the investigators have developed a novel acupuncture stimulation mode called dense cranial electroacupuncture stimulation (DCEAS), in which electrical stimulation is directly delivered on dense acupoints (6-8 pairs in general) located on the forehead innervated by the trigeminal sensory pathway. This pathway has intimate afferent fibers projecting the brainstem reticular formation, a pivotal brain region containing serotonin (5-HT) and norepinephrine (NE) neuronal cells involved in the processing of mood signals. neuroanatomic rationale for DCEAS is that electrical stimulation on dense scalp acupoints could enhance the activities of brainstem nuclei containing 5-HT and NE neuronal systems via the trigeminal sensory nucleus, and then modulate brain regions related to mood processing (Zhang et al., 2012).Our serial clinical studies have demonstrated the effectiveness of DCEAS and alike modes in patients with major depression, postpartum depression, insomnia and obsessive compulsive disorder (Chung et al., 2012; 2014; Huang et al., 2004, 2005; Qu et al., 2013; Zhang et al., 2009, 2012a). Most recently, our pilot study further confirms that DCEAS is effective in reducing stroke patients' depressive symptoms; a combination of DCEAS and body acupuncture (CAI) is more effective in reducing neuropsychiatric sequelae of stroke (Man et al., 2014). These encouraging results warrant a large-scale controlled trial.

The pathogenesis of PSD is mainly associated with decreased serotonin (5-HT) and norepinephrine (NE) function in the brain (Gustafson et al., 1995). On the other hand, neuro-anatomic rationale for DCEAS is that electrical stimulation on dense scalp acupoints could enhance the activities of brainstem nuclei containing 5-HT and NE neuronal systems via the trigeminal sensory nucleus, and then modulate brain regions related to mood processing (Zhang et al., 2012b). Based on these studies, the investigators hypothesize that CAI could yield better treatment outcomes in improving PSD compared to Least acupuncture stimulation (LAS) control.

An apparent advantage of TCM clinical practice is individualized or personalized treatment, i.e., treatment protocol is tailored to meet individual's current clinical manifestations and different stages of illness, termed differentiation syndromes. Previous studies have suggested a potential relationship between the therapeutic efficacy of acupuncture and TCM syndromes of PSD (Dang, 2013; Wu, 2010; Xin et al., 2005). The investigators will further determine whether there are correlates of TCM syndromes of PSD with the CAI treatment.

The working hypothesis of the proposed study is that CAI is an effective intervention in improving PSD and comorbid symptoms often observed in stroke patients. To test this hypothesis, an 8-week, assessor-blind, randomized, controlled trial will be proposed to determine: (1) whether the patients treated with the CAI could produce significantly greater improvement than those treated with LAS and (2) whether there are correlates of TCM syndromes of PSD with the CAI treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: October 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 80 Years

Eligibility

Inclusion Criteria:

1. men or women aged 35 to 80 years old;

2. diagnosed as ischemic or haemorrhagic stroke within 18 months, confirmed with cerebral computed topographic scanning or magnetic resonance imaging; and

3. developed significant depressive episode, with score of 16 or greater in the 17-item Hamilton Rating Scale for Depression (HAMD-17) and depression has lasted at least 2 weeks.

Exclusion Criteria:

1. presence of severe aphasia, especially fluent aphasia;

2. presence of severe cognitive dysfunction, as indicated by the Mini-mental State Examination (MMSE) score < 18;

3. history of psychiatric illness other than depression;

4. presence of another chronic disorder, including severe Parkinson's disease, cardiac disease, cancers, epilepsy, or chronic alcoholism;

5. having impaired hepatic or renal function; or (6) having bleeding tendency.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Stroke
• Stroke Sequelae

Intervention

Procedure:
• Dense cranial electroacupuncture stimulation
DCEAS is a novel stimulation mode in which electrical stimulation is delivered on acupoints located on the forehead. Six pairs of acupoints are used: Baihui (GV20, +) and Yintang (EX-HN3, -), left Sishencong (EX-HN1, -) and Toulinqi (GB15, +), right Sishencong (EX-HN1, -) and Toulinqi (GB15, +), bilateral Shuaigu (GB8, L+, R-), bilateral Taiyang (EX-HN5, L+, R-), and bilateral Touwei (ST8, L+, R-). Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation, followed by electrical stimulation (ITO ES-160, continuous waves at 2 Hz, 100 µs).
• Body acupuncture
Following acupoints are used: Shui-Gou (GV26), Shen-Men (HT7). He-Gu (LI4), Qu-Chi (LI11), Guan-Yuan (CV4), Zu-San-Li (ST36), Feng-Long (ST40) and San-Yin-Jiao (SP6). Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation at 15 min. No electrical stimulation is delivered.

Drug:
• Antidepressant
Patients will continue their existing antidepressant therapy as usual. Treatment regimens may be further adjusted during 8 weeks of study, depending upon physicians' discretion.

Other:
• Rehabilitation
Patients will continue their existing rehabilitation therapy as usual. Treatment regimens may be further adjusted during 8 weeks of study, depending upon physicians' discretion.

Procedure:
• Least acupuncture stimulation
The acupoints chosen are less related to the treated syndromes based on Traditional Chinese Medicine (TCM) theory; the number of acupoints used and the intensity of electrical stimulation are also lower than the comprehensive acupuncture regimen. The following 6 acupoints will be used in LAS control: bilateral Tong-Tian (BI7, L+, R-), bilateral Shou San-Li (LI10) and bilateral Fu-Yang (BL59). Electrical stimulation will be only performed on bilateral Tong-Tian (BI7) and the intensities are adjusted to a level at which patients just start feeling the stimulation.

Locations

Country	Name	City	State
Hong Kong	Department of Rehabilitation, Kowloon Hospital	Kowloon
Hong Kong	Division of Rehabilitation Medicine, Tung Wah Hospital.	Sheung Wan

Sponsors (3)

Lead Sponsor	Collaborator
The University of Hong Kong	Kowloon Hospital, Hong Kong, Tung Wah Hospital

Country where clinical trial is conducted

Hong Kong, 

References & Publications (26)

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Chung KF, Yeung WF, Yu YM, Yung KP, Zhang SP, Zhang ZJ, Wong MT, Lee WK, Chan LW. Acupuncture for residual insomnia associated with major depressive disorder: a placebo- and sham-controlled, subject- and assessor-blind, randomized trial. J Clin Psychiatry. 2015 Jun;76(6):e752-60. doi: 10.4088/JCP.14m09124. — View Citation

Chung KF, Yeung WF, Zhang ZJ, Yung KP, Man SC, Lee CP, Lam SK, Leung TW, Leung KY, Ziea ET, Taam Wong V. Randomized non-invasive sham-controlled pilot trial of electroacupuncture for postpartum depression. J Affect Disord. 2012 Dec 15;142(1-3):115-21. doi: 10.1016/j.jad.2012.04.008. Epub 2012 Jul 26. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in depression measured by HAMD-17	Depression will be measured using the Hamilton Rating Scale for Depression (HAMD-17). Assessments will be conducted at baseline and once monthly thereafter.	Baseline, 4 week, 8 week
Primary	Changes in depression measured by MADRS	Depression will be measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). Assessments will be conducted at baseline and once monthly thereafter.	Baseline, 4 week, 8 week
Primary	Changes in depression measured by SDS	Depression will be measured using the Zung Self-Rating Depression Scale (SDS). Assessments will be conducted at baseline and once monthly thereafter.	Baseline, 4 week, 8 week
Primary	Changes in locomotor function measured by BI	Locomotor function will be measured using the Barthel Index of Activities of Daily Living (BI). Assessments will be conducted at baseline and once monthly thereafter.	Baseline, 4 week, 8 week
Primary	Changes in cognitive function	The Montreal Cognitive Assessment (MoCA) will be used as an objective measurement for subjects' cognitive function. Assessments will be conducted at baseline and once monthly thereafter.	Baseline, 4 week, 8 week
Secondary	Clinical outcome of treatment	It includes clinical response, defined as <50% reduction at endpoint from baseline on HAMD-17, and remission, defined as 7 points or less on HAMD-17 score.	8 week
Secondary	Emergence of adverse events	Adverse events are assessed using the Treatment Emergent Symptom Scale (TESS).	Baseline, 4 week, 8 week
Secondary	TCM syndrome diagnosis	To determine Traditional Chinese Medicine (TCM) syndrome correlated of the treatment efficacy, the investigators will conduct TCM syndrome diagnosis. The 5 most common syndromes of PSD are listed below: Liver Depression with Qi-stagnation; Liver Depression with Spleen deficiency; Blood stasis and phlegm obstruction; Deficiency of Both Heart and Spleen; or; Deficiency of Both Liver and Kidney Yin.	Baseline