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Comment on “Shiatsu as an Adjuvant Therapy for Depression in Patients With Alzheimer’s Disease: A Pilot Study”



Recently, there has been increasing interest toward nonpharmacological approaches for dementia and associated clinical manifestations, such as depression, with the common goal to improve health and quality of life of both patients and caregivers. In this scenario, the role of Shiatsu is of clinical and research interest, although to date a definitive recommendation on a systematic use in clinical practice cannot be made. To overcome the heterogeneity of the previous studies, we tested Shiatsu as an add-on treatment for late-life depression in a dedicated community of patients with mild-to-moderate Alzheimer’s disease. We found a significant adjuvant effect of Shiatsu for depression in these patients and hypothesized a neuroendocrine-mediated action on the neural circuits implicated in mood and affect regulation. However, this finding must be considered preliminary and requires confirmation in larger-scale controlled studies, possibly extending the range of outcome measures and including predictors of response. Future investigations should also include an objective assessment of the hypothalamus-pituitary-adrenocortical axis functioning. Nevertheless, starting from this pilot study, we suggest that a customized protocol applied for an adequate period in a controlled sample will represent a non-invasive and feasible advance for promoting patients’ mood and, possibly, slowing cognitive decline.
Comment on “Shiatsu as an Adjuvant
Therapy for Depression in Patients With
Alzheimer’s Disease: A Pilot Study”
Giuseppe Lanza, MD, PhD
, Stella Silvia Centonze, BSc
Gera Destro, MD
, Veronica Vella, MD, PhD
Maria Bellomo, MD, PhD
, Manuela Pennisi, MD, PhD
Rita Bella, MD
, and Domenico Ciavardelli, PhD
Recently, there has been increasing interest toward nonpharmacological approaches for dementia and associated clinical manifes-
tations, such as depression, with the common goal to improve health and quality of life of both patients and caregivers. In this
scenario, the role of Shiatsu is of clinical and research interest, although to date a definitive recommendation on a systematic use in
clinical practice cannot be made. To overcome the heterogeneity of the previous studies, we tested Shiatsu as an add-on treatment
for late-life depression in a dedicated community of patients with mild-to-moderate Alzheimer’s disease. We found a significant
adjuvant effect of Shiatsu for depression in these patients and hypothesized a neuroendocrine-mediated action on the neural circuits
implicated in mood and affect regulation. However, this finding must be considered preliminary and requires confirmation in larger-
scale controlled studies, possibly extending the range of outcome measures and including predictors of response. Future investi-
gations should also include an objective assessment of the hypothalamus-pituitary-adrenocortical axis functioning. Nevertheless,
starting from this pilot study, we suggest that a customized protocol applied for an adequate period in a controlled sample will
represent a non-invasive and feasible advance for promoting patients’ mood and, possibly, slowing cognitive decline.
alternative medicine, cognitive function, dementia, depression, health services
Received October 1, 2018. Accepted for publication December 26, 2018.
More than 35 billion people worldwide have dementia and the
number is rapidly rising with increased longevity. More than
90%of these subjects experience behavioral and psychological
symptoms, including agitation, irritability, anxiety, apathy, and
depression, particularly in the mid-to-late stage of the disease.
These symptoms significantly distress not only patients but
also families and care staff.
Recently, mood disorders in cog-
nitively impaired elderly people has generated considerable
attention. Particularly, late-life depression is frequently associ-
ated with apathy and emotional lability, thus significantly wor-
sening the burden of care.
Management is traditionally based
on pharmacological intervention. While antidepressant and
antipsychotic medications may offer control of some symp-
toms, they have a number of potential side effects, mainly due
to the hypersensitivity of the aging brain, the decreased hepatic
and kidney drug metabolism, and the complex and often
unpredictable interactions with other drugs concomitantly
taken. As such, doses require regular adjustments and different
drugs are frequently changed.
Oasi Research Institute–IRCCS, Troina, Italy
University “Kore” of Enna, Enna, Italy
Ospedale “Michele Chiello”, ASP 4, Piazza Armerina, Italy
University of Catania “Garibaldi-Nesima Medical Center”, Catania, Italy
Emergency Hospital “Cannizzaro”, Catania, Italy
Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele, Catania,
Centro Scienze dell’Invecchiamento e Medicina Traslazionale–CeSI-Met,
Chieti, Italy
Corresponding Author:
Giuseppe Lanza, MD, PhD, Oasi Research Institute–IRCCS, Via Conte
Ruggero, 73-94018, Troina, Italy.
Journal of Evidence-Based Integrative Medicine
Volume 24: 1-4
ªThe Author(s) 2019
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In recent years, there has been an increased interest toward
the possibility of nonpharmacological approaches against
dementia and associated clinical manifestations, with the com-
mon goal to improve cognition, mood, behavior, and, ulti-
mately, quality of life.
Regarding depression, an effective
management of mood disorder means to improve the global
health of patients and caregivers, reduce distress, avoid inap-
propriate medications, enable positive relationships and activ-
ities, delay institutionalization, and be cost-effective. In this
scenario, the potential effect of Shiatsu, a popular technique
of complementary and alternative medicine based on the prin-
ciples of traditional Chinese medicine, is of increasing clinical
interest. Basically, Shiatsu consists of pressure and scrubbing
of the energy pathways in the body based on knowledge and
application of traditional Chinese medicine to treat and relieve
pain and a wide spectrum of pain-related symptoms. Although
the most common indications are muscular-skeletal and psy-
chological problems, Shiatsu is actually a holistic therapy and,
as such, it also affects the patient’s well-being, lifestyle, diet,
sleep, and body-mind awareness.
The working mechanism of Shiatsu and similar techniques
(such as acupressure) are not fully known, but they can be
explained by different theories. Traditional Chinese medicine
speculates that acupressure stimulates the acupoints to enhance
energy flowing along the meridians, achieving therapeutic out-
comes by improving the functions of the body systems.
chemical studies show that stimulation of the acupoints is able
to induce complex neurohormonal responses; one of these may
involve the hypothalamus-pituitary-adrenocortical axis in
counteracting the overproduction of cortisol, thus promoting
a relaxation response.
Accordingly, similar manipulative
therapies, such as massage and therapeutic touch, were shown
to be useful in lowering patients’ stress and cortisol after treat-
Finally, abnormal synaptic plasticity has been widely
documented in depression and in both animal models and
patients with Alzheimer’s disease.
In this context, the
release of neuromodulators after Shiatsu might improve corti-
cal plasticity and, consequently, mood and cognition.
Although previous studies regarding Shiatsu and acupres-
sure stressed their effects in decreasing behavioral symptoms,
few of these employed a rigorous study design. Of these inves-
tigations, two only used a standardized protocol and objective
measurement of effectiveness.
The other studies had a
number of limitations, such as a subjective determination in
deciding whether the treatment was effective, the small sample
size, a non-double-blind design, and the lack of standardized
protocols. Moreover, although only one study has recently pro-
posed a standardized protocol,
clinical experience has
demonstrated that it is difficult for formal caregivers to adhere
to a twice-a-day treatment schedule in long-term care facilities.
In addition, despite the growing interest in its use, there is a
need to examine Shiatsu in daily clinical practice and, where
appropriate, to develop test protocols and specific training pro-
grams for the health care staff. Finally, to further increase the
evidences for Shiatsu in dementia and late-life depression, the
available data should be carefully reviewed and the quality of
the published studies critically analyzed.
To date, a definitive recommendation on a systematic use of
Shiatsu in clinical practice cannot be made. In 2011, Robinson
et al
investigated the evidence of positive effects of Shiatsu
and acupressure on behavior and psychological symptoms of
dementia. The authors identified 40 randomized controlled
clinical trials, 8 controlled clinical trials, 5 crossover trials, 6
within-participants studies, 1 observational study, 10 uncon-
trolled studies, and 1 prospective study. Overall, agitation,
aggression, and nonaggressive behavior all declined signifi-
cantly in demented patients, further supporting the clinical
application of Shiatsu. However, a conclusive evidence of effi-
cacy is still lacking, and while much of the research is of
insufficient quality to translate into practice, the high-quality
evidence for pain, postoperative nausea and vomiting, and
sleep may be of use to Shiatsu or acupressure practitioners.
On the other hand, the research on this topic is still very much
in its infancy, and the practitioners need to work closely with
both clinicians and researchers to build up a larger body of
evidence. Given the prevalence of Shiatsu worldwide, the need
for high quality research is imperative, and practitioners should
be encouraged to engage in research using well-designed and
reported studies, in particular with large and controlled
To overcome the heterogeneity of the previous studies and
some of the aforementioned limitations, we first tested Shiatsu
as an add-on treatment for late-life depression in a dedicated
community of patients with mild-to-moderate Alzheimer’s dis-
In a group of 12 participants, in addition to standard
pharmacological and physical interventions, once-weekly
Shiatsu treatment for 10 months produced a significant
improvement of a mood score scale in 6 subjects randomly
selected. Although we found a within-group improvement of
all the outcome measures considered (cognition, mood, and
functional status), the analysis of differences before and after
the interventions showed a statistically significant amelioration
only of depression in patients undergoing Shiatsu þphysical
activity compared with those practicing physical activity
We concluded for an adjuvant effect of Shiatsu for
depression in patients with Alzheimer’s disease and hypothe-
size that the underlying pathomechanism might involve the
neuroendocrine-mediated action of Shiatsu on neural circuits
implicated in mood and affect regulation. We also provided
experimental evidence that an integrated approach based on
drug therapy, physical activity, and Shiatsu may be a feasible
way to slow down affective decline in patients with Alzhei-
mer’s disease and to alleviate the caregivers’ burden of care.
However, such a complex approach cannot easily allow to
“quantify” how much improvement was due to Shiatsu itself
or to the stimulation provided by the interactions among these
Overall, this was a pilot study that should be viewed in lights
of a number of limitations, including the very small sample
size, the unbalanced sex distribution, the limited number of
psychopathological tests used, the lack of double blinding, and
2Journal of Evidence-Based Integrative Medicine
the absence of a follow-up after the end of the protocol.
Moreover, given that participants came from the same commu-
nity, contamination between the 2 groups cannot be ruled out,
although narrow differences between experimental and control
group outcomes would be expected. Finally, as usual in similar
studies, the improvement produced by Shiatsu might, at least in
part, be due to a placebo effect provided by the caring attention
of dedicated therapist who induces a sense of calm and positive
anticipation. For these reasons, the finding must be considered
preliminary given that it requires confirmation and cross-
validation in larger-scale controlled studies, possibly extending
the range of outcome measures and predictors of response.
Moreover, exploring the mechanisms behind the effect of
Shiatsu by including the measurement of other variables (such
as pain, agitation, diet, and sleep) appears worthy of investiga-
tion in future studies and predictive of useful additional data.
Future studies should also elucidate whether Shiatsu and acu-
pressure reduce depression in people with dementia through an
objective assessment of hypothalamus-pituitary-adrenocortical
axis functioning.
Despite the limitations, however, some counterarguments
should be considered. First, the recruitment of cohorts of suit-
able sample size is inherently difficult in the case of these
patients given the need for proxy consent, the occurrence of
complex comorbidities, and the high rate of hospitalization,
thus reducing the opportunity to recruit or retain participants
in complex controlled trials. Second, blinding is always a chal-
lenge in the assessment of all kinds of nonpharmacologic ther-
apeutic interventions, where the comparison treatment must
somehow mimic the study treatment while maintaining blind-
Yet without the rigorous methodology of a carefully
randomized and placebo-controlled double-blinded study, the
suspicion will remain that the apparent therapeutic effect
obtained by Shiatsu (or by other forms of alternative/comple-
mentary medicine) is actually a nonspecific or placebo effect
produced by cultivating the patient’s optimistic expectations in
the context of a good therapeutic relationship.
Third, long-
itudinal studies are recommended to investigate the long-term
effects of Shiatsu on cognitive and psychological variables. In
this frame, findings from our study provide references for
future clinical trials in terms of sample size estimation and
recruitment strategies, optimal protocol dosage to be used, out-
come measurement and timing to be considered, as well as
strategies of data collection and intervention implementation.
Based on our study and literature review, we can propose
some key recommendations for practitioners. First, the limited
evidence currently available suggests the strong need for a
more rigorous research. Second, investigators using a rando-
mized controlled trial design need to ensure that they strictly
adhere to the principles of randomized controlled trial design
itself, namely the random assignment of participants to treat-
ment or control groups and the blinding of data collectors; after
randomization, the 2 groups need to be followed up in exactly
the same way, and the only difference should be the treatment
being compared. Third, because symptoms, severity, and
course of depression differ from person to person, it is
important to consider the individual responses to the interven-
tion. Finally, Shiatsu or other nonpharmacological options
should be compared with pharmacological therapies in order
to prioritize treatments.
In conclusion, the finding from our study
suggests that
Shiatsu may play a role in promoting psychological well-
being of dementing patients. Further investigations with
large-scale and methodologically robust design are recom-
mended to produce stronger evidence for application of cost-
effective interventions. The high prevalence of both depression
and dementia in the elderly highlights the treatment gap cur-
rently present among these patients. As known, mood and other
psychological symptoms in patients with dementia are influ-
enced by many pathophysiological and biopsychosocial fac-
tors, so that Shiatsu, integrated with other therapeutic
options, might reveal even greater effectiveness. Promoting
psychophysical wellness will increase patients’ compliance to
cognitive rehabilitation, improve quality of life, and reduce the
negative outcomes related to disease complications and dis-
tress. Starting from this study,
we suggest that a customized
Shiatsu protocol applied for an adequate period of time in a
large controlled sample will represent a useful and noninvasive
advance for promoting not only an improvement of patients’
mood but, possibly, also a slowing of cognitive decline.
Author Contributions
GL and SSC conceptualized the study. MP and RB performed the
literature review. GL and VV were involved with writing the original
draft. GD and DC were involved in the writing, review, and editing of
the article. MB supervised the study. All authors approved the final
version of the paper.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
The authors received no financial support for the research, authorship,
and/or publication of this article.
Giuseppe Lanza, MD, PhD
Ethical Approval
Not applicable.
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4Journal of Evidence-Based Integrative Medicine
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Background . Transcranial magnetic stimulation (TMS) highlighted functional changes in dementia, whereas there are few data in patients with vascular cognitive impairment-no dementia (VCI-ND). Similarly, little is known about the neurophysiological impact of vascular depression (VD) on deterioration of cognitive functions. We test whether depression might affect not only cognition but also specific cortical circuits in subcortical vascular disease. Methods . Sixteen VCI-ND and 11 VD patients, age-matched with 15 controls, underwent a clinical-cognitive, neuroimaging, and TMS assessment. After approximately two years, all participants were prospectively reevaluated. Results . At baseline, a significant more pronounced intracortical facilitation (ICF) was found in VCI-ND patients. Reevaluation revealed an increase of the global excitability in both VCI-ND and VD subjects. At follow-up, the ICF of VCI-ND becomes similar to the other groups. Only VD patients showed cognitive deterioration. Conclusions . Unlike VD, the hyperfacilitation found at baseline in VCI-ND patients suggests enhanced glutamatergic neurotransmission that might contribute to the preservation of cognitive functioning. The hyperexcitability observed at follow-up in both groups of patients also indicates functional changes in glutamatergic neurotransmission. The mechanisms enhancing the risk of dementia in VD might be related either to subcortical vascular lesions or to the lack of compensatory functional cortical changes.
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Clinical and functional studies consider major depression (MD) and vascular depression (VD) as different neurobiological processes. Hypoexcitability of the left frontal cortex to transcranial magnetic stimulation (TMS) is frequently reported in MD, whereas little is known about the effects of TMS in VD. Thus, we aimed to assess and compare motor cortex excitability in patients with VD and MD. Eleven VD patients, 11 recurrent drug-resistant MD patients, and 11 healthy controls underwent clinical, neuropsychological and neuroimaging evaluations in addition to bilateral resting motor threshold, cortical silent period, and paired-pulse TMS curves of intracortical excitability. All patients continued on psychotropic drugs, which were unchanged throughout the study. Scores on one of the tests evaluating frontal lobe abilities (Stroop Color-Word interference test) were worse in patients compared with controls. The resting motor threshold in patients with MD was significantly higher in the left hemisphere compared with the right (p < 0.05), and compared with the VD patients and controls. The cortical silent period was bilaterally prolonged in MD patients compared with VD patients and controls, with a statistically significant difference in the left hemisphere (p < 0.01). No differences were observed in the paired-pulse curves between patients and controls. This study showed distinctive patterns of motor cortex excitability between late-onset depression with subcortical vascular disease and early-onset recurrent drug resistant MD. The data provide a TMS model of the different processes underlying VD and MD. Additionally, our results support the "Vascular depression hypothesis" at the neurophysiological level, and confirm the inter-hemispheric asymmetry to TMS in patients with MD. We were unable to support previous findings of impaired intracortical inhibitory mechanisms to TMS in patients with MD, although a drug-induced effect on our results cannot be excluded. This study may aid the understanding of the pathogenetic differences underlying the clinical spectrum of depressive disorders.
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Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors occurring in subjects with dementia. BPSD constitute a major component of the dementia syndrome irrespective of its subtype. They are as clinically relevant as cognitive symptoms as they strongly correlate with the degree of functional and cognitive impairment. BPSD include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite changes. It is estimated that BPSD affect up to 90% of all dementia subjects over the course of their illness, and is independently associated with poor outcomes, including distress among patients and caregivers, long term hospitalization, misuse of medication and increased health care costs. Although these symptoms can be present individually it is more common that various psychopathological features co-occur simultaneously in the same patient. Thus, categorization of BPSD in clusters taking into account their natural course, prognosis and treatment response may be useful in the clinical practice. The pathogenesis of BPSD has not been clearly delineated but it is probably the result of a complex interplay of psychological, social and biological factors. Recent studies have emphasized the role of neurochemical, neuropathological and genetic factors underlying the clinical manifestations of BPSD. A high degree of clinical expertise is crucial to appropriately recognize and manage the neuropsychiatric symptoms in a patient with dementia. Combination of non-pharmacological and careful use of pharmacological interventions is the recommended therapeutic for managing BPSD. Given the modest efficacy of current strategies, there is an urgent need to identify novel pharmacological targets and develop new non-pharmacological approaches to improve the adverse outcomes associated with BPS.
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Shiatsu, similar to acupressure, uses finger pressure, manipulations and stretches, along Traditional Chinese Medicine meridians. Shiatsu is popular in Europe, but lacks reviews on its evidence-base. Acupressure and Shiatsu clinical trials were identified using the MeSH term 'acupressure' in: EBM reviews; AMED; BNI; CINAHL; EMBASE; MEDLINE; PsycARTICLES; Science Direct; Blackwell Synergy; Ingenta Select; Wiley Interscience; Index to Theses and ZETOC. References of articles were checked. Inclusion criteria were Shiatsu or acupressure administered manually/bodily, published after January 1990. Two reviewers performed independent study selection and evaluation of study design and reporting, using standardised checklists (CONSORT, TREND, CASP and STRICTA). Searches identified 1714 publications. Final inclusions were 9 Shiatsu and 71 acupressure studies. A quarter were graded A (highest quality). Shiatsu studies comprised 1 RCT, three controlled non-randomised, one within-subjects, one observational and 3 uncontrolled studies investigating mental and physical health issues. Evidence was of insufficient quantity and quality. Acupressure studies included 2 meta-analyses, 6 systematic reviews and 39 RCTs. Strongest evidence was for pain (particularly dysmenorrhoea, lower back and labour), post-operative nausea and vomiting. Additionally quality evidence found improvements in sleep in institutionalised elderly. Variable/poor quality evidence existed for renal disease symptoms, dementia, stress, anxiety and respiratory conditions. Appraisal tools may be inappropriate for some study designs. Potential biases included focus on UK/USA databases, limited grey literature, and exclusion of qualitative and pre-1989 studies. Evidence is improving in quantity, quality and reporting, but more research is needed, particularly for Shiatsu, where evidence is poor. Acupressure may be beneficial for pain, nausea and vomiting and sleep.
Objectives: Among the complementary and alternative medicine, Shiatsu might represent a feasible option for depression in Alzheimer's disease (AD). We evaluated Shiatsu on mood, cognition, and functional independence in patients undergoing physical activity. Design: Single-blind randomized controlled study. Setting: Dedicated Community Center for patients with AD. Interventions: AD patients with depression were randomly assigned to the "active group" (Shiatsu + physical activity) or the "control group" (physical activity alone). Shiatsu was performed by the same therapist once a week for ten months. Main outcome measures: Global cognitive functioning (Mini Mental State Examination - MMSE), depressive symptoms (Geriatric Depression Scale - GDS), and functional status (Activity of Daily Living - ADL, Instrumental ADL - IADL) were assessed before and after the intervention. Results: We found a within-group improvement of MMSE, ADL, and GDS in the active group. However, the analysis of differences before and after the interventions showed a statistically significant decrease of GDS score only in the active group. Conclusions: The combination of Shiatsu and physical activity improved depression in AD patients compared to physical activity alone. The pathomechanism might involve neuroendocrine-mediated effects of Shiatsu on neural circuits implicated in mood and affect regulation.
OBJECTIVES: To explore the effectiveness of acupressure and Montessori-based activities in decreasing the agitated behaviors of residents with dementia. DESIGN: A double-blinded, randomized (two treatments and one control; three time periods) cross-over design was used. SETTING: Six special care units for residents with dementia in long-term care facilities in Taiwan were the sites for the study. PARTICIPANTS: One hundred thirty-three institutionalized residents with dementia. INTERVENTION: Subjects were randomized into three treatment sequences: acupressure-presence-Montessori methods, Montessori methods-acupressure-presence and presence-Montessori methods-acupressure. All treatments were done once a day, 6 days per week, for a 4-week period. MEASUREMENT: The Cohen-Mansfield Agitation Inventory, Ease-of-Care, and the Apparent Affect Rating Scale. RESULTS: After receiving the intervention, the acupressure and Montessori-based-activities groups saw a significant decrease in agitated behaviors, aggressive behaviors, and physically nonaggressive behaviors than the presence group. Additionally, the ease-of-care ratings for the acupressure and Montessori-based-activities groups were significantly better than for the presence group. In terms of apparent affect, positive affect in the Montessori-based-activities group was significantly better than in the presence group. CONCLUSION: This study confirms that a blending of traditional Chinese medicine and a Western activities program would be useful in elderly care and that in-service training for formal caregivers in the use of these interventions would be beneficial for patients.