Can Acupuncture Treat Post-stroke Depression?
Condition: Stroke; Depression; Stroke Sequelae
MeSH terms: Stroke; Depression; Depressive Disorder
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Dense cranial electroacupuncture stimulation; Body acupuncture; Antidepressant; Rehabilitation; Least acupuncture stimulation
Intervention type(s): Procedure; Procedure; Drug; Other; Procedure
Intervention description(s): 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).; 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.; Patients will continue their existing antidepressant therapy as usual. Treatment regimens may be further adjusted during 8 weeks of study, depending upon physicians' discretion.; Patients will continue their existing rehabilitation therapy as usual. Treatment regimens may be further adjusted during 8 weeks of study, depending upon physicians' discretion.; 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.
Other intervention name(s): DCEAS; BA; Rehab; LAS
Intervention MeSH terms: Antidepressive Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: stroke; depression; stroke sequelae; acupuncture; DCEAS; CAI; LAS