Ignite Creation Date:
2024-05-05 @ 5:17 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00425399
Status:
COMPLETED
Last Update Posted:
2014-05-22
First Post:
2007-01-22
Brief Title:
Shiatsu Adjuvant Therapy For Schizophrenia
Sponsor:
Herzog Hospital
Organization:
Herzog Hospital
Study Overview
Official Title:
Shiatsu Adjuvant Therapy for Hospitalized Psychiatric Patients an Open Pilot Study
Status:
COMPLETED
Status Verified Date:
2009-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In the current study we will study the effect of adding shiatsu treatment to conventional therapy in work with hospitalized schizophrenic patients
The hypotheses of this study are several
1 Shiatsu can improve the patients symptoms
2 Shiatsu can ameliorate neuromuscular side effects produced by standard anti-psychotic treatment
3 Shiatsu can provide patients with tools to deal with the stresses of their illness
2 Methodology We propose an open pilot study in which a total of 20 patients of both sexes will be enrolled These patients will be drawn from the inpatient psychiatric wards at Herzog Hospital
Upon inclusion into the trial all participants will receive shiatsu treatment consisting of two individual weekly 40-minute shiatsu treatment sessions for four weeks Provider and patient will be of the same gender Standard pharmacotherapy will be provided as needed during the treatment period Medication and dosage will not be changed If necessary benzodiazepines will be administered as required
Outcome measures
The following assessments will be included
1 Medication Use of SOS benzodiazepines
2 Clinical rating scales PANSS CGI NOSIE Hamilton Scales for depression and anxiety
1 Side effect scales Simpson Angus Scale AIMS scale UKU scale 2 Neurophysiological testing Prepulse inhibition PPI 3 Neurocognitive testing This will be performed using the NIMHs Measurement and Treatment Research to Improve Cognition in Schizophrenia MATRICS Consensus Cognitive Battery for Clinical Trials
The hypotheses of this study are several
1 Shiatsu can improve the patients symptoms
2 Shiatsu can ameliorate neuromuscular side effects produced by standard anti-psychotic treatment
3 Shiatsu can provide patients with tools to deal with the stresses of their illness
2 Methodology We propose an open pilot study in which a total of 20 patients of both sexes will be enrolled These patients will be drawn from the inpatient psychiatric wards at Herzog Hospital
Upon inclusion into the trial all participants will receive shiatsu treatment consisting of two individual weekly 40-minute shiatsu treatment sessions for four weeks Provider and patient will be of the same gender Standard pharmacotherapy will be provided as needed during the treatment period Medication and dosage will not be changed If necessary benzodiazepines will be administered as required
Outcome measures
The following assessments will be included
1 Medication Use of SOS benzodiazepines
2 Clinical rating scales PANSS CGI NOSIE Hamilton Scales for depression and anxiety
1 Side effect scales Simpson Angus Scale AIMS scale UKU scale 2 Neurophysiological testing Prepulse inhibition PPI 3 Neurocognitive testing This will be performed using the NIMHs Measurement and Treatment Research to Improve Cognition in Schizophrenia MATRICS Consensus Cognitive Battery for Clinical Trials
Detailed Description:
SHIATSU ADJUVANT THERAPY FOR SCHIZOPHRENIA Protocol for an Open Pilot Study
1 Background Schizophrenia is a severe chronic mental illness that affects approximately 1 of the population worldwide While the pharmacological treatments available have advanced considerably in the last fifty years there are limits to what they offer some patients especially in terms of improving dysphoria sleep mood avolition social functioning and anhedonia which contribute greatly to the everyday misery of these patients
Furthermore some of the antipsychotic drugs induce side effects of parkinsonism akathisias orofacial dyskinesias dystonias and their associated muscle pain and stiffness The treatments used for those side effects are anticholinergic drugs eg trihexyphenidyl benzodiazepines and beta blockers The number and variety of such drugs suggests what clinicians know to be unfortunately true there are no magic bullets for these symptoms These drugs are also not innocent causing side effects of their own contributing to polypharmacy and carrying a financial cost
Schizophrenia then remains a debilitating illness whose treatment results are often partial and may produce unpleasant side-effects New approaches to supplement standard modalities ought to be considered
Shiatsu or acupressure is a holistic form of medicine originating in Japan but now widely practiced throughout the world Shiatsu involves applying pressure to meridians of the body much like acupuncture but without the needles The shiatsu therapist views the whole body as interconnected - stiffness in one part may reflect a problem in another or emotional disharmony In accordance with the WHO definition of health as a state of complete physical mental and social well-being and not merely the absence of disease or infirmity shiatsu massage aims to improve the overall well-being of its recipients by manipulating the body
Shiatsu theory is based on traditional Chinese medicine which posits meridians of life force chi running through the body and aims to optimize health through manipulating the body into maximal alignment Disease according to this approach is as an accumulation of damage and stress that causes the body to tense up in various areas leading to health disturbances The treatment aims to loosen tense muscles and tendons and restore balance to the body
Shiatsu also involves a diagnostic process that is designed to locate sources of problems The main four areas of this process are the patients appearance hisher voice the specific complaints and medical history of the patient and touch diagnosis The touch is meant to reveal areas of excess or lack of energy in the body or internal organs and autonomic nervous system Treatment is individualized according to the findings of this examination
Goals of treatment in addition to releasing muscle and tendon tension and protecting these structures are to help the patient acquire an awareness of his or her body and psyche in order to avoid recurrence of the problems to identify life stressors mental and physical and to strengthen the patients overall energy flow and resilience to disease
The two fields of shiatsu are do-in and anma Do-in are the exercises that involve stretching parts of the body combined with breathing exercises in order to loosen tense joints and improve general circulation Anma shiatsu is the more familiar massage-type treatment However it is not performed for comfort or pleasure as in Western massage but rather as a type of medical treatment It is performed with a fully dressed patient with direct pressure applied with the practitioners fingers Both diagnosis and treatment are performed this way with the findings of the exam directing further actions
How might the effects of shiatsu be explained in terms of Western medicine In order to answer this we will consider research done not only for shiatsu but for acupuncture as well which has been more extensively examined This is justified for two reasons first of all shiatsu and acupuncture share the same understanding of human functioning and disease including the core concepts of chi and meridians and accordingly they recognize the same points along the body for applying pressure shiatsu or needles acupuncture Secondly in studies which have been conducted to test the effectiveness of alternative remedies acupressure and acupuncture have often been combined eg Vachiramon Wang 2005 Melchart et al 2006
2 Biological basis for shiatsu Medical research has attempted to understand how Chinese medicine works its effects Several theories have been developed which may be of relevance to schizophrenia
1 Endorphins The most established effect of acupuncture is the release of endorphins which are endogenous opioid neuropeptides Hökfelt 1991 Sjölund et al 1977 Endorphin release appears to be closely related to the analgesic effects of acupuncture Endorphins also promote a general feel of well being and reduction of tension which can have salutary effects in treating mental illness
2 Cytokines Cytokines mediate the inflammatory response They also promote endorphin release by the pituitary Van der Meer et al 1996 Drzyzga et al 2006 have reviewed the possible connection between cytokines on the one hand and neuropathological changes schizophrenia and anti-psychotic medication mechanisms of action on the other A growing body of evidence suggests that cytokinins mediate neuropathological changes in schizophrenia and the antipsychotic effects of medication Acupuncture has been shown to affect the cytokine system in animal Liu et al 2004 and human Petti et al 2002 studies The cytokine system is theoretically a pathway through which acupuncture could produce therapeutic effects upon schizophrenia
3 Glutamatergic mechanisms gained prominence as an important factor in the pathogenesis and treatment of schizophrenia In experiments with animals N-methyl-D-aspartic acid NMDA receptor antagonists have synergistically enhanced the anti-nociceptive effects of electro-acupuncture Zhang et al 2002 Assessing the relationship between glutamatergic activity and acupuncture effects could provide important information about therapeutic mechanisms of action
4 Neuropeptide Y NPY NPYs role in the CNS is not well understood However appreciation for the possible role of NPY in the pathogenesis of severe mental disorder has increased in recent years NPY mRNA levels were significantly reduced in the frontal cortex of patients with both schizophrenia and bipolar disorder Kuromitsu et al 2001 NPY has also been shown to play a role in mediating the effects of antipsychotic medication in both animal Huang et al 2006 and human studies Obuchowicz et al 2004 Interestingly the effects of NPY may be mediated by glutamatergic mechanisms Rosse Deutsch 2004 This is relevant to our study because NPY levels in saliva have been found to increase following acupuncture treatment Dawidson et al 1998 This then is another possible mechanism through which acupuncture can be clinically relevant to the treatment of schizophrenia
Studies have already been carried out to assess the effectiveness of Chinese medicine in the treatment of schizophrenia In a recent review of five studies in the Cochrane Database Rathbone Xia 2005 acupuncture as adjuvant therapy provided with anti-psychotic medication showed some evidence of improved outcomes on clinical rating scales and side effect profiles though overall the evidence was deemed insufficient to reach a definite conclusion and more comprehensive and better designed studies were recommended
A second review Moffet 2006 of clinical trials of acupuncture for various medical disorders made the important observation that too often no meaningful physiological rationale is provided for the proposed effectiveness of the treatment Proposing a rationale enables the investigator to suggest a testable causal hypothesis which can contribute to our knowledge of the techniques mechanism of action
In the current study we will focus on assessments of the glutamatergic system by neurophysiological prepulse inhibition testing using prepulse inhibition PPI In this paradigm the subject is presented with an auditory stimulus or pre-pulse which would not ordinarily cause the subject to blink Following this initial prepulse by a tenth of a second comes a second louder stimulus the pulse which would cause blinking were it not preceded by the prepulse Pre-pulse inhibition a measure of sensory gating or filtering is determined by the reduction in blink response to a pulse following a pre-pulse as compared to the blink response without the preparatory pre-pulse Prepulse inhibition of the startle response which has been reliably demonstrated in both humans and animals rev in Braff et al 2001 Swerdlow et al 2001 is a preattentive automatic process
Schizophrenia patients have been repeatedly shown reduced inhibition of the startle reflex in PPI rev in Geyer et al 2001 This loss of normal PPI is thought to be a measure of the deficient sensorimotor gating Braff and Geyer 1990 that underlies sensory flooding and cognitive fragmentation in these patients McGhie and Chapman 1961 Furthermore some studies report that PPI deficits may correlate with symptoms severity or cognitive and functional impairment in schizophrenia and may partially or completely resolve with antipsychotic drugs treatment rev in Braff et al 2001
One of the proposed models of PPI hypothesizes the involvement of glutamatergic mainly N-methyl-D-aspartate receptor NMDAR-mediated neurotransmission Glutamate is a key inhibitory neurotransmitter Glutamatergic neurotransmission may correlate with the efficiency of sensory gating Swerdlow and Geyer 1999 Glutamatergic synapses have been implicated in the regulation of PPI in rodents Swerdlow et al 2001
In light of the possible connection between PPI and the glutamatergic system we decided to administer PPI to the subjects before and after the shiatsu treatment in order to assess whether any ameliorating effect of shiatsu which as noted can involve glutamatergic mechanisms may correlate with changes in the PPI
We will also assess neurocognitive function using a battery of tests developed specifically for use in assessing patients with schizophrenia
3 Study goals Based upon the rationales we suggested for utilizing shiatsu in the treatment of schizophrenia and based upon the studies which have already been performed we are proposing a pilot study to examine the efficacy of shiatsu as adjuvant therapy for antipsychotics in the treatment of patients with schizophrenia
The goals of this study are several
1 To improve the patients symptoms 2 To ameliorate neuromuscular side effects produced by standard anti-psychotic treatment 3 To provide patients with tools to deal with the stresses of their illness 4 To provide a basis for further investigation of the effects of shiatsu 4 Methodology We propose an open pilot study in which a total of 20 patients will be enrolled These patients will be drawn from the inpatient psychiatric wards at Herzog Hospital They will be recruited by the treating physicians at these facilities All patients would be fully informed of the experimental treatments goals and possible outcomes Either the participant or where relevant the court-appointed guardian will be required to provide informed consent Participants will of course be free to discontinue their participation for any reason at any time
41 Inclusion Criteria
1 DSM-IV-R diagnosis of schizophrenia or schizoaffective disorder
2 Ages 18 and over
3 Clinical status stable as reflected by at least one month of drug treatment without change of anti-psychotic drug or dosage
4 Ability to cooperate with 40-minute sessions 42 Exclusion Criteria
-- --
1 Active fracture or other orthopedic problem
2 Skin condition that renders treatment unsafe or painful
3 Active infection in skin or soft tissues such as cellulitis
4 Any acute illness or other medical condition eg solid tissue malignancy for which shiatsu may be contraindicated
43 Study design Upon inclusion into the trial all participants will receive shiatsu treatment consisting of two individual weekly 40-minute shiatsu treatment sessions for four weeks The shiatsu providers are all trained and certified by Tsabar College an alternative medicine training institute and all have at least two years of post-training experience in shiatsu Each patient will receive all treatments from the same provider for the duration of his or her treatment Provider and patient will be of the same gender The patient is clothed with a shirt and full-length trousers or skirt during shiatsu Treatment will not include contact with sensitive regions of the body such as the chest in work with females pelvic or inner thigh regions or any other region of the body with which the patient is not comfortable
Standard pharmacotherapy will be provided as needed during the treatment period Medication and dosage will not be changed If necessary benzodiazepines will be administered as required
44 Rescue strategies and withdrawal from research In case of exacerbation defined as an increase of 2 points on the BPRS or 4 to 6 on the individual items listed above or of one point on the CGI the patient may receive clothiapine at a dose of up to 80 mgday for not more than 3 days within a 14-day period
In case of relapse defined as an increase of 3 points on the BPRS or from 5 to 7 on somatic concern conceptual disorganization hostility suspiciousness hallucinatory behavior or unusual thought content or of 2 points on the CGI the patient will be withdrawn from the study and appropriate treatment instituted Furthermore if the patient deteriorates clinically in a way that may be related to treatment eg paranoid fantasies directed towards the shiatsu therapist the research protocol for that individual will be discontinued
Significant emergent medical problems will also lead to the withdrawal of the patient from the research
45 Outcome measures
The following assessments will be included
1 Medication
a Use of SOS benzodiazepines quantity and frequency
2 Clinical rating scales
1 PANSS
2 CGI
3 NOSIE
4 Hamilton Scales for depression and anxiety
2 Side effect scales
1 Simpson Angus Scale
2 AIMS scale
3 UKU scale 3 Neurophysiological testing Prepulse inhibition PPI This is performed as follows The eyeblink component of the acoustic startle reflex is measured using electromyography of the obicularis oculi muscle Two electrodes 6 mm AgAgCl electrodes filled with electrode gel parker laboratories inc will be positioned below and to the right of the patients right eye over the obicularis oculi muscle Electrodes will be placed to minimize potential electro-oculogram artifact Specifically 1 electrode will be placed approximately 1 cm lateral to and 05 cm below the lateral canthus and the second electrode will be placed approximately 15 cm below and slightly medial to the first electrode conforming to the location of the obicularis oculi fibers A ground electrode will be placed behind the right ear over the mastoid All resistances will be less than 10 kOhm Electrodes will be fixed to the skin as close as possible to each other using adhesive collars All acoustic stimuli will be delivered binaurally through headphones Maico TDH-39-P Subjects will be seated comfortably in a softly lit after they will be informed of the procedure The prepulse and startle stimuli are bursts of white noise with a fixed interstimulus intervals of 30 60 and 120 ms for measuring PPI or 15 ms and 4500 ms for measuring PPF The startle session will begin with a 5-minute acclimation period of 70-dB white noise which will continue throughout the session followed by six trial blocks Block 1 consisted of six pulse-alone trials Blocks 2 and 3 each consisted of 32 trials containing 8 pulse-alone and 24 prepulse-pulse trials presented in pseudorandom order Block 4 consisted of six pulse-alone trials Block 5 consisted of six pulse-alone trials and 12 prepulse-pulse trials and block 6 consisted six pulse alone trials The first forth and sixth blocks will measure habituation as well as startle response the second and the third blocks will measure startle response and PPI and the fifth block will measure PPF The pulse alone stimulus is a 40 ms presentation of 115dB white noise the prepulse stimulus is a 20 ms except the 15 ms interval stimulus which lasts 5 ms presentation of 86 dB noise both over 70 dB of continuous background noise Acoustic stimuli consist of pulse alone prepulse and pulse or no stimulus trials and are presented in a fixed pseudorandom order Electromyographic activity recorded by the electrodes will be directed through a customized electromyographic amplifier to a computerized startle response monitoring system for digitization and analysis SR-LAB San Diego Instruments Inc San Diego Calif The system will record 1000 one-ms readings starting at the onset of the startle stimulus Acoustic startle and prepulse stimuli will be presented binaurally through headphones
4 Neurocognitive testing This will be performed using the NIMHs Measurement and Treatment Research to Improve Cognition in Schizophrenia MATRICS Consensus Cognitive Battery for Clinical Trials This recently-developed battery is recommended for use in clinical trials of putative cognition-enhancing agents in schizophrenia The MATRICS battery including Hebrew translations of relevant tests is presently used in the Stanley Foundation-sponsored Israel Multicenter D-Serine Trial IMSER Dr Heresco-Levy - Co-Principal Investigator and will be implemented by a trained psychologist presently participating in this project
5 Hypothesis Shiatsu adjuvant therapy will improve psychiatric and motor symptoms in patients after four weeks of therapy
61 Potential Benefits Shiatsu treatment is a pleasant experience involving applying pressure manually to various points of the body Furthermore the research will itself lead to more time spent by staff with patients which is to the patients benefit Beyond that we anticipate that shiatsu will be of benefit alongside the standard pharmacological treatment which will be continued in enhancing the patients wellbeing and reducing medication side effects
62 Potential Adverse Effects Shiatsu is not known to carry any significant risks to patients It may rarely cause soreness muscle cramps or local pain Patients will be informed of this possibility and instructed to notify the shiatsu therapist if discomfort occurs during treatment Psychological distress may be aroused by the human contact and touching that occurs during treatment Patients will be advised about this possibility as well Patients wishing for any reason to discontinue the research will of course be withdrawn from the study
63 Significance of study The treatment of schizophrenia could benefit from new modalities to complement existing approaches To date no study has systemically evaluated the use of shiatsu in treating schizophrenia and only one study has evaluated shiatsu in this population for drug induced myospasm Due to the chronic nature of this disease and the severe impairment of quality of life any and all means should be sought in combating the suffering inherent in this disease Shiatsu may be a cost-effective pleasant and well-tolerated treatment for some schizophrenia symptoms This study may pave the way for similar studies in other psychiatric patients
7 References Braff DL Geyer MA 1990 Sensorimotor gating and schizophrenia human and animal model studies Archives of General Psychiatry 47 181-188
Braff DL Geyer MA Swerdlow NR 2001 Human studies of prepulse inhibition of startle normal subjects patient groups and pharmacological studies Psychopharmacology 156 234-258
Dawidson I Angmar-Månsson B Blom M Theodorsson E Lundeberg T The influence of sensory stimulation acupuncture on the release of neuropeptides in the saliva of healthy subjects Life Sciences 1998 63 659-674 Drzyzga L Obuchowicz E Marcinowska A Herman ZS Cytokines in schizophrenia and the effects of antipsychotic drugs Brain Behav Immun 2006 Geyer MA Krebs-Thomson K Braff DL Swerdlow NR 2001 Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia a decade in review Psychopharmacology 156 117-154
Hökfelt T Neuropeptides in perspective the last ten years Neuron 1991 7 867879
Huang XF Deng C Zavitsanou KNeuropeptide Y mRNA expression levels following chronic olanzapine clozapine and haloperidol administration in rats Neuropeptides 2006 Jun403213-9
Liu XY Zhou HF Pan YL Liang XB Niu DB Xue B Li FQ He QH Wang XH Wang XM Electro-acupuncture stimulation protects dopaminergic neurons from inflammation-mediated damage in medial forebrain bundle-transected rats Exp Neurol 2004 1891189-96
McGhie A Chapman J 1961 Disorders of attention and perception in early schizophrenia British Journal of Medical Psychology 34 102-116
Melchart D Ihbe-Heffinger A Leps B von Schilling C Linde K Acupuncture and acupressure for the prevention of chemotherapy-induced nausea--a randomised cross-over pilot study Support Care Cancer 2006 Aug148878-82
Moffet HH How might acupuncture work A systematic review of physiologic rationales from clinical trials BMC Complementary and Alternative Medicine 2006 6 25-32
Obuchowicz E Krysiak R Herman ZS Does neuropeptide Y NPY mediate the effects of psychotropic drugs Neurosci Biobehav Rev 2004 Oct286595-610
Petti FB Liguori A Ippoliti F J Tradit Chin Med Study on cytokines IL-2 IL-6 IL-10 in patients of chronic allergic rhinitis treated with acupuncture 2002222104-11
Rathbone J Xia J Acupuncture for schizophrenia Cochrane Database Syst Rev 2005 4CD005475
Rosse RB Deutsch SI The Yoking of glutamatergic brain mechanisms involved in controlling brain neuronal excitability and psychosis to brain mechanisms involved in appetite regulation a new hypothesis on the origin of psychosis Med Hypotheses 2004623406-12
Sjölund B Terenius L Erickson M Increased cerebrospinal fluid levels of endorphins after electro-acupuncture Acta Physiol Scand 1977 100 382384
Swerdlow NR Geyer MA 1999 Neurophysiology and neuropharmacology of short lead interval startle modification In Dawson ME Schell AM Eds Startle Modification Implications for Neuroscience Cognitive Science and Clinical Science pp 114-133 New York Cambridge University Press
Swerdlow NR Geyer MA Braff DL 2001 Neural circuitry of prepulse inhibition of startle in the rat current knowledge and future challenges Psychopharmacology 156 1940-215
Vachiramon A Wang WC Acupuncture and acupressure techniques for reducing orthodontic post-adjustment pain J Contemp Dent Pract 2005 61163-7
Van der Meer M J Hermans A R Pesman G J Sweep C G Effect of cytokines on pituitary beta endorphin and adrenal corticosterone release in vitro Cytokine 1996 8 238247
Zhang YQ Ji GC Wu GC Zhao ZQ Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats Pain 2002993525-35
1 Background Schizophrenia is a severe chronic mental illness that affects approximately 1 of the population worldwide While the pharmacological treatments available have advanced considerably in the last fifty years there are limits to what they offer some patients especially in terms of improving dysphoria sleep mood avolition social functioning and anhedonia which contribute greatly to the everyday misery of these patients
Furthermore some of the antipsychotic drugs induce side effects of parkinsonism akathisias orofacial dyskinesias dystonias and their associated muscle pain and stiffness The treatments used for those side effects are anticholinergic drugs eg trihexyphenidyl benzodiazepines and beta blockers The number and variety of such drugs suggests what clinicians know to be unfortunately true there are no magic bullets for these symptoms These drugs are also not innocent causing side effects of their own contributing to polypharmacy and carrying a financial cost
Schizophrenia then remains a debilitating illness whose treatment results are often partial and may produce unpleasant side-effects New approaches to supplement standard modalities ought to be considered
Shiatsu or acupressure is a holistic form of medicine originating in Japan but now widely practiced throughout the world Shiatsu involves applying pressure to meridians of the body much like acupuncture but without the needles The shiatsu therapist views the whole body as interconnected - stiffness in one part may reflect a problem in another or emotional disharmony In accordance with the WHO definition of health as a state of complete physical mental and social well-being and not merely the absence of disease or infirmity shiatsu massage aims to improve the overall well-being of its recipients by manipulating the body
Shiatsu theory is based on traditional Chinese medicine which posits meridians of life force chi running through the body and aims to optimize health through manipulating the body into maximal alignment Disease according to this approach is as an accumulation of damage and stress that causes the body to tense up in various areas leading to health disturbances The treatment aims to loosen tense muscles and tendons and restore balance to the body
Shiatsu also involves a diagnostic process that is designed to locate sources of problems The main four areas of this process are the patients appearance hisher voice the specific complaints and medical history of the patient and touch diagnosis The touch is meant to reveal areas of excess or lack of energy in the body or internal organs and autonomic nervous system Treatment is individualized according to the findings of this examination
Goals of treatment in addition to releasing muscle and tendon tension and protecting these structures are to help the patient acquire an awareness of his or her body and psyche in order to avoid recurrence of the problems to identify life stressors mental and physical and to strengthen the patients overall energy flow and resilience to disease
The two fields of shiatsu are do-in and anma Do-in are the exercises that involve stretching parts of the body combined with breathing exercises in order to loosen tense joints and improve general circulation Anma shiatsu is the more familiar massage-type treatment However it is not performed for comfort or pleasure as in Western massage but rather as a type of medical treatment It is performed with a fully dressed patient with direct pressure applied with the practitioners fingers Both diagnosis and treatment are performed this way with the findings of the exam directing further actions
How might the effects of shiatsu be explained in terms of Western medicine In order to answer this we will consider research done not only for shiatsu but for acupuncture as well which has been more extensively examined This is justified for two reasons first of all shiatsu and acupuncture share the same understanding of human functioning and disease including the core concepts of chi and meridians and accordingly they recognize the same points along the body for applying pressure shiatsu or needles acupuncture Secondly in studies which have been conducted to test the effectiveness of alternative remedies acupressure and acupuncture have often been combined eg Vachiramon Wang 2005 Melchart et al 2006
2 Biological basis for shiatsu Medical research has attempted to understand how Chinese medicine works its effects Several theories have been developed which may be of relevance to schizophrenia
1 Endorphins The most established effect of acupuncture is the release of endorphins which are endogenous opioid neuropeptides Hökfelt 1991 Sjölund et al 1977 Endorphin release appears to be closely related to the analgesic effects of acupuncture Endorphins also promote a general feel of well being and reduction of tension which can have salutary effects in treating mental illness
2 Cytokines Cytokines mediate the inflammatory response They also promote endorphin release by the pituitary Van der Meer et al 1996 Drzyzga et al 2006 have reviewed the possible connection between cytokines on the one hand and neuropathological changes schizophrenia and anti-psychotic medication mechanisms of action on the other A growing body of evidence suggests that cytokinins mediate neuropathological changes in schizophrenia and the antipsychotic effects of medication Acupuncture has been shown to affect the cytokine system in animal Liu et al 2004 and human Petti et al 2002 studies The cytokine system is theoretically a pathway through which acupuncture could produce therapeutic effects upon schizophrenia
3 Glutamatergic mechanisms gained prominence as an important factor in the pathogenesis and treatment of schizophrenia In experiments with animals N-methyl-D-aspartic acid NMDA receptor antagonists have synergistically enhanced the anti-nociceptive effects of electro-acupuncture Zhang et al 2002 Assessing the relationship between glutamatergic activity and acupuncture effects could provide important information about therapeutic mechanisms of action
4 Neuropeptide Y NPY NPYs role in the CNS is not well understood However appreciation for the possible role of NPY in the pathogenesis of severe mental disorder has increased in recent years NPY mRNA levels were significantly reduced in the frontal cortex of patients with both schizophrenia and bipolar disorder Kuromitsu et al 2001 NPY has also been shown to play a role in mediating the effects of antipsychotic medication in both animal Huang et al 2006 and human studies Obuchowicz et al 2004 Interestingly the effects of NPY may be mediated by glutamatergic mechanisms Rosse Deutsch 2004 This is relevant to our study because NPY levels in saliva have been found to increase following acupuncture treatment Dawidson et al 1998 This then is another possible mechanism through which acupuncture can be clinically relevant to the treatment of schizophrenia
Studies have already been carried out to assess the effectiveness of Chinese medicine in the treatment of schizophrenia In a recent review of five studies in the Cochrane Database Rathbone Xia 2005 acupuncture as adjuvant therapy provided with anti-psychotic medication showed some evidence of improved outcomes on clinical rating scales and side effect profiles though overall the evidence was deemed insufficient to reach a definite conclusion and more comprehensive and better designed studies were recommended
A second review Moffet 2006 of clinical trials of acupuncture for various medical disorders made the important observation that too often no meaningful physiological rationale is provided for the proposed effectiveness of the treatment Proposing a rationale enables the investigator to suggest a testable causal hypothesis which can contribute to our knowledge of the techniques mechanism of action
In the current study we will focus on assessments of the glutamatergic system by neurophysiological prepulse inhibition testing using prepulse inhibition PPI In this paradigm the subject is presented with an auditory stimulus or pre-pulse which would not ordinarily cause the subject to blink Following this initial prepulse by a tenth of a second comes a second louder stimulus the pulse which would cause blinking were it not preceded by the prepulse Pre-pulse inhibition a measure of sensory gating or filtering is determined by the reduction in blink response to a pulse following a pre-pulse as compared to the blink response without the preparatory pre-pulse Prepulse inhibition of the startle response which has been reliably demonstrated in both humans and animals rev in Braff et al 2001 Swerdlow et al 2001 is a preattentive automatic process
Schizophrenia patients have been repeatedly shown reduced inhibition of the startle reflex in PPI rev in Geyer et al 2001 This loss of normal PPI is thought to be a measure of the deficient sensorimotor gating Braff and Geyer 1990 that underlies sensory flooding and cognitive fragmentation in these patients McGhie and Chapman 1961 Furthermore some studies report that PPI deficits may correlate with symptoms severity or cognitive and functional impairment in schizophrenia and may partially or completely resolve with antipsychotic drugs treatment rev in Braff et al 2001
One of the proposed models of PPI hypothesizes the involvement of glutamatergic mainly N-methyl-D-aspartate receptor NMDAR-mediated neurotransmission Glutamate is a key inhibitory neurotransmitter Glutamatergic neurotransmission may correlate with the efficiency of sensory gating Swerdlow and Geyer 1999 Glutamatergic synapses have been implicated in the regulation of PPI in rodents Swerdlow et al 2001
In light of the possible connection between PPI and the glutamatergic system we decided to administer PPI to the subjects before and after the shiatsu treatment in order to assess whether any ameliorating effect of shiatsu which as noted can involve glutamatergic mechanisms may correlate with changes in the PPI
We will also assess neurocognitive function using a battery of tests developed specifically for use in assessing patients with schizophrenia
3 Study goals Based upon the rationales we suggested for utilizing shiatsu in the treatment of schizophrenia and based upon the studies which have already been performed we are proposing a pilot study to examine the efficacy of shiatsu as adjuvant therapy for antipsychotics in the treatment of patients with schizophrenia
The goals of this study are several
1 To improve the patients symptoms 2 To ameliorate neuromuscular side effects produced by standard anti-psychotic treatment 3 To provide patients with tools to deal with the stresses of their illness 4 To provide a basis for further investigation of the effects of shiatsu 4 Methodology We propose an open pilot study in which a total of 20 patients will be enrolled These patients will be drawn from the inpatient psychiatric wards at Herzog Hospital They will be recruited by the treating physicians at these facilities All patients would be fully informed of the experimental treatments goals and possible outcomes Either the participant or where relevant the court-appointed guardian will be required to provide informed consent Participants will of course be free to discontinue their participation for any reason at any time
41 Inclusion Criteria
1 DSM-IV-R diagnosis of schizophrenia or schizoaffective disorder
2 Ages 18 and over
3 Clinical status stable as reflected by at least one month of drug treatment without change of anti-psychotic drug or dosage
4 Ability to cooperate with 40-minute sessions 42 Exclusion Criteria
-- --
1 Active fracture or other orthopedic problem
2 Skin condition that renders treatment unsafe or painful
3 Active infection in skin or soft tissues such as cellulitis
4 Any acute illness or other medical condition eg solid tissue malignancy for which shiatsu may be contraindicated
43 Study design Upon inclusion into the trial all participants will receive shiatsu treatment consisting of two individual weekly 40-minute shiatsu treatment sessions for four weeks The shiatsu providers are all trained and certified by Tsabar College an alternative medicine training institute and all have at least two years of post-training experience in shiatsu Each patient will receive all treatments from the same provider for the duration of his or her treatment Provider and patient will be of the same gender The patient is clothed with a shirt and full-length trousers or skirt during shiatsu Treatment will not include contact with sensitive regions of the body such as the chest in work with females pelvic or inner thigh regions or any other region of the body with which the patient is not comfortable
Standard pharmacotherapy will be provided as needed during the treatment period Medication and dosage will not be changed If necessary benzodiazepines will be administered as required
44 Rescue strategies and withdrawal from research In case of exacerbation defined as an increase of 2 points on the BPRS or 4 to 6 on the individual items listed above or of one point on the CGI the patient may receive clothiapine at a dose of up to 80 mgday for not more than 3 days within a 14-day period
In case of relapse defined as an increase of 3 points on the BPRS or from 5 to 7 on somatic concern conceptual disorganization hostility suspiciousness hallucinatory behavior or unusual thought content or of 2 points on the CGI the patient will be withdrawn from the study and appropriate treatment instituted Furthermore if the patient deteriorates clinically in a way that may be related to treatment eg paranoid fantasies directed towards the shiatsu therapist the research protocol for that individual will be discontinued
Significant emergent medical problems will also lead to the withdrawal of the patient from the research
45 Outcome measures
The following assessments will be included
1 Medication
a Use of SOS benzodiazepines quantity and frequency
2 Clinical rating scales
1 PANSS
2 CGI
3 NOSIE
4 Hamilton Scales for depression and anxiety
2 Side effect scales
1 Simpson Angus Scale
2 AIMS scale
3 UKU scale 3 Neurophysiological testing Prepulse inhibition PPI This is performed as follows The eyeblink component of the acoustic startle reflex is measured using electromyography of the obicularis oculi muscle Two electrodes 6 mm AgAgCl electrodes filled with electrode gel parker laboratories inc will be positioned below and to the right of the patients right eye over the obicularis oculi muscle Electrodes will be placed to minimize potential electro-oculogram artifact Specifically 1 electrode will be placed approximately 1 cm lateral to and 05 cm below the lateral canthus and the second electrode will be placed approximately 15 cm below and slightly medial to the first electrode conforming to the location of the obicularis oculi fibers A ground electrode will be placed behind the right ear over the mastoid All resistances will be less than 10 kOhm Electrodes will be fixed to the skin as close as possible to each other using adhesive collars All acoustic stimuli will be delivered binaurally through headphones Maico TDH-39-P Subjects will be seated comfortably in a softly lit after they will be informed of the procedure The prepulse and startle stimuli are bursts of white noise with a fixed interstimulus intervals of 30 60 and 120 ms for measuring PPI or 15 ms and 4500 ms for measuring PPF The startle session will begin with a 5-minute acclimation period of 70-dB white noise which will continue throughout the session followed by six trial blocks Block 1 consisted of six pulse-alone trials Blocks 2 and 3 each consisted of 32 trials containing 8 pulse-alone and 24 prepulse-pulse trials presented in pseudorandom order Block 4 consisted of six pulse-alone trials Block 5 consisted of six pulse-alone trials and 12 prepulse-pulse trials and block 6 consisted six pulse alone trials The first forth and sixth blocks will measure habituation as well as startle response the second and the third blocks will measure startle response and PPI and the fifth block will measure PPF The pulse alone stimulus is a 40 ms presentation of 115dB white noise the prepulse stimulus is a 20 ms except the 15 ms interval stimulus which lasts 5 ms presentation of 86 dB noise both over 70 dB of continuous background noise Acoustic stimuli consist of pulse alone prepulse and pulse or no stimulus trials and are presented in a fixed pseudorandom order Electromyographic activity recorded by the electrodes will be directed through a customized electromyographic amplifier to a computerized startle response monitoring system for digitization and analysis SR-LAB San Diego Instruments Inc San Diego Calif The system will record 1000 one-ms readings starting at the onset of the startle stimulus Acoustic startle and prepulse stimuli will be presented binaurally through headphones
4 Neurocognitive testing This will be performed using the NIMHs Measurement and Treatment Research to Improve Cognition in Schizophrenia MATRICS Consensus Cognitive Battery for Clinical Trials This recently-developed battery is recommended for use in clinical trials of putative cognition-enhancing agents in schizophrenia The MATRICS battery including Hebrew translations of relevant tests is presently used in the Stanley Foundation-sponsored Israel Multicenter D-Serine Trial IMSER Dr Heresco-Levy - Co-Principal Investigator and will be implemented by a trained psychologist presently participating in this project
5 Hypothesis Shiatsu adjuvant therapy will improve psychiatric and motor symptoms in patients after four weeks of therapy
61 Potential Benefits Shiatsu treatment is a pleasant experience involving applying pressure manually to various points of the body Furthermore the research will itself lead to more time spent by staff with patients which is to the patients benefit Beyond that we anticipate that shiatsu will be of benefit alongside the standard pharmacological treatment which will be continued in enhancing the patients wellbeing and reducing medication side effects
62 Potential Adverse Effects Shiatsu is not known to carry any significant risks to patients It may rarely cause soreness muscle cramps or local pain Patients will be informed of this possibility and instructed to notify the shiatsu therapist if discomfort occurs during treatment Psychological distress may be aroused by the human contact and touching that occurs during treatment Patients will be advised about this possibility as well Patients wishing for any reason to discontinue the research will of course be withdrawn from the study
63 Significance of study The treatment of schizophrenia could benefit from new modalities to complement existing approaches To date no study has systemically evaluated the use of shiatsu in treating schizophrenia and only one study has evaluated shiatsu in this population for drug induced myospasm Due to the chronic nature of this disease and the severe impairment of quality of life any and all means should be sought in combating the suffering inherent in this disease Shiatsu may be a cost-effective pleasant and well-tolerated treatment for some schizophrenia symptoms This study may pave the way for similar studies in other psychiatric patients
7 References Braff DL Geyer MA 1990 Sensorimotor gating and schizophrenia human and animal model studies Archives of General Psychiatry 47 181-188
Braff DL Geyer MA Swerdlow NR 2001 Human studies of prepulse inhibition of startle normal subjects patient groups and pharmacological studies Psychopharmacology 156 234-258
Dawidson I Angmar-Månsson B Blom M Theodorsson E Lundeberg T The influence of sensory stimulation acupuncture on the release of neuropeptides in the saliva of healthy subjects Life Sciences 1998 63 659-674 Drzyzga L Obuchowicz E Marcinowska A Herman ZS Cytokines in schizophrenia and the effects of antipsychotic drugs Brain Behav Immun 2006 Geyer MA Krebs-Thomson K Braff DL Swerdlow NR 2001 Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia a decade in review Psychopharmacology 156 117-154
Hökfelt T Neuropeptides in perspective the last ten years Neuron 1991 7 867879
Huang XF Deng C Zavitsanou KNeuropeptide Y mRNA expression levels following chronic olanzapine clozapine and haloperidol administration in rats Neuropeptides 2006 Jun403213-9
Liu XY Zhou HF Pan YL Liang XB Niu DB Xue B Li FQ He QH Wang XH Wang XM Electro-acupuncture stimulation protects dopaminergic neurons from inflammation-mediated damage in medial forebrain bundle-transected rats Exp Neurol 2004 1891189-96
McGhie A Chapman J 1961 Disorders of attention and perception in early schizophrenia British Journal of Medical Psychology 34 102-116
Melchart D Ihbe-Heffinger A Leps B von Schilling C Linde K Acupuncture and acupressure for the prevention of chemotherapy-induced nausea--a randomised cross-over pilot study Support Care Cancer 2006 Aug148878-82
Moffet HH How might acupuncture work A systematic review of physiologic rationales from clinical trials BMC Complementary and Alternative Medicine 2006 6 25-32
Obuchowicz E Krysiak R Herman ZS Does neuropeptide Y NPY mediate the effects of psychotropic drugs Neurosci Biobehav Rev 2004 Oct286595-610
Petti FB Liguori A Ippoliti F J Tradit Chin Med Study on cytokines IL-2 IL-6 IL-10 in patients of chronic allergic rhinitis treated with acupuncture 2002222104-11
Rathbone J Xia J Acupuncture for schizophrenia Cochrane Database Syst Rev 2005 4CD005475
Rosse RB Deutsch SI The Yoking of glutamatergic brain mechanisms involved in controlling brain neuronal excitability and psychosis to brain mechanisms involved in appetite regulation a new hypothesis on the origin of psychosis Med Hypotheses 2004623406-12
Sjölund B Terenius L Erickson M Increased cerebrospinal fluid levels of endorphins after electro-acupuncture Acta Physiol Scand 1977 100 382384
Swerdlow NR Geyer MA 1999 Neurophysiology and neuropharmacology of short lead interval startle modification In Dawson ME Schell AM Eds Startle Modification Implications for Neuroscience Cognitive Science and Clinical Science pp 114-133 New York Cambridge University Press
Swerdlow NR Geyer MA Braff DL 2001 Neural circuitry of prepulse inhibition of startle in the rat current knowledge and future challenges Psychopharmacology 156 1940-215
Vachiramon A Wang WC Acupuncture and acupressure techniques for reducing orthodontic post-adjustment pain J Contemp Dent Pract 2005 61163-7
Van der Meer M J Hermans A R Pesman G J Sweep C G Effect of cytokines on pituitary beta endorphin and adrenal corticosterone release in vitro Cytokine 1996 8 238247
Zhang YQ Ji GC Wu GC Zhao ZQ Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats Pain 2002993525-35
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
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Is a PPSD?:
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Is a US Export?:
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Is an FDA AA801 Violation?:
None