- Email: [email protected]
Hypnosis for Postradiation Xerostomia in Head and Neck Cancer Patients: A Pilot Study
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Journal of Pain and Symptom Management
Vol. 37 No. 6 June 2009
Clinical Note
Hypnosis for Postradiation Xerostomia in Head and Neck Cancer Patients: A Pilot Study Elad Schiff, MD, Jorge G. Mogilner, MD, Eyal Sella, MD, Ilana Doweck, MD, Oded Hershko, MD, Eran Ben-Arye, MD, and Noam Yarom, MD Department of Internal Medicine (E.S.), Bnai Zion Medical Center, Haifa; Department for Complementary/Integrative Medicine, Law and Ethics (E.S.), and The International Center for Health, Law and Ethics (E.S.), Haifa University, Haifa; Department of Pediatric Surgery (J.G.M.), The Ruth & Bruce Rappaport Faculty of Medicine, and the Complementary and Traditional Medicine Unit (E.B.-A.), Department of Family Medicine, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa; Department of Otolaryngology-Head and Neck Surgery (E.S., I.D.), Carmel Medical Center, Haifa, Israel; Faculty of Medicine (O.H.), Semmelweis University, Budapest, Hungary; Clalit Health Services (E.B.-A.), Haifa and Western Galilee District; and Oral Medicine Clinic (N.Y.), Department of Oral and Maxillofacial Surgery, Sheba Medical Center, Tel-Hashomer, Israel
Abstract Xerostomia, the sensation of dry mouth, affects almost all patients who undergo radiotherapy for cancer in the head and neck area. Current therapies for xerostomia are inadequate, and the condition negatively impacts the quality of life. This prospective observational pilot study aimed to evaluate whether hypnosis could improve salivation and decrease xerostomia. Twelve patients with xerostomia after radiotherapy for head and neck cancer were assessed for severity of xerostomia symptoms and sialometry. They then received a single hypnosis session with specific suggestions to increase salivation. The session was recorded on a compact disk (CD), and the participants were instructed to listen to it twice a day for one month. Sialometry was repeated immediately after hypnosis. Validated xerostomia questionnaires were completed at one, four, and 12 weeks after hypnosis. A substantial overall improvement was reported by eight patients at 12 weeks (66%). The saliva flow rate increased on sialometry in nine patients following hypnosis (75%). There was no correlation between the magnitude of changes in the measured saliva flow rate and changes in subjective measures (Spearman’s correlation coefficient r ¼ 0.134). Symptomatic improvement significantly correlated with the number of times the patients listened to the hypnosis CD (r ¼ 0.714, P ¼ 0.009). No adverse events were reported. The data from this small observational trial suggest that hypnosis may be an effective treatment for xerostomia. Confirmation in a larger randomized and controlled investigation is warranted. J Pain Symptom Manage 2009;37:1086e1092. Ó 2009 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Keywords Xerostomia, dry mouth, radiation, salivation, hypnosis
Dr. Elad Schiff and Dr. Jorge G. Mogilner contributed equally to the study. Address correspondence to: Elad Schiff, MD, Department of Internal Medicine B, Bnai Zion Medical Ó 2009 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved.
Center, P.O. Box 4940, Haifa 31048, Israel. E-mail: [email protected] Accepted for publication: July 25, 2008.
0885-3924/09/$esee front matter doi:10.1016/j.jpainsymman.2008.07.005
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Hypnosis for Postradiation Xerostomia in Head and Neck Cancer
Introduction Each year, approximately 43,000 people are diagnosed with head and neck cancer in the United States.1 Many patients receive radiation therapy delivered to the head and neck area, which results in injury to salivary glands, eventually leading to little or no saliva production. The amount of salivary flow reduction depends on the radiation dose and fractional size, as well as the volume of salivary glands irradiated.2 Up to 100% of patients receiving radical radiotherapy develop some degree of xerostomia, the subjective sensation of dryness of the mouth. They also may have oral discomfort and pain, greatly increased susceptibility to dental caries, frequent oral infections, and difficulty in speaking, chewing, and swallowing. These outcomes can lead to severe oral disease, nutritional deficiencies, and an overall decline in quality of life.3 There are few treatment options for alleviating xerostomia in these patients. Salivary substitutes and sialogogues, such as pilocarpine,4 are often tried. Submandibular gland transfer,5 acupuncture,6 and acupuncture-like transcutaneous nerve stimulation7 have been suggested. These treatment modalities have shown various degrees of effectiveness and diverse side effects. Xerostomia continues to have a substantial negative impact on the quality of life of survivors of head and neck cancer.8 Medical hypnosis is the clinical application of hypnosis to medical disorders and procedures. As defined by the American Psychological Association, a hypnotic procedure is used to encourage and evaluate responses to suggestions.9 Kihlstrom described hypnosis as ‘‘a set of procedures in which a person designated as the hypnotherapist suggests that another person (the patient or subject) experience various changes in sensation, perception, cognition, or control over behavior.’’10 Others, such as Kirsch and Lynn,11 described hypnosis as simply ‘‘a heightened state of relaxation or a state of focused attention.’’ More recently, hypnosis has been conceptualized as a set of behavioral techniques.12 A hypnotic session usually has an induction phase and an application phase. During the induction phase, the individual begins to enter a hypnotic state, during which there are few competing cognitive demands and less self-
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reflective thought.13 This allows suggestibility, which is defined as ‘‘communication that is accepted uncritically.’’14 During the application phase, specific suggestions are provided according to the treatment goals. Logistically, hypnosis is done in live sessions with a hypnotherapist facilitating the process. Another commonly used technique is teaching self-hypnosis at a formal session with a hypnotherapist, during which individuals learn how to enter the hypnotic state on their own. To achieve the latter goal, sessions are often recorded for regular practice at the client’s home.15 Whether facilitated by a hypnotherapist or carried out by the subjects themselves, it is generally agreed that all hypnosis is, in fact, selfhypnosis. Several mechanisms have been suggested to explain how hypnosis exerts its effects. Electroencephalographic studies of hypnotic states show very slow high-range theta waves (5e7 Hz), which are typically associated with loss of executive control and reflect massive cortical inhibition.16 On the other hand, when the hypnotic state involves specific stimulatory sensory or motor suggestions, the relevant sensory and motor areas of the brain may be activated even more than they are during nonhypnotic conditions.17 Salivation can be conditioned, as described in the classic studies by Pavlov.18 Seeing certain foods or just thinking about food can trigger salivation in an expectant manner.19 The anticipation of food, which constitutes the cephalic phase of alimentary secretions, has an effect on the magnitude of salivation. Subjects will demonstrate more salivation when they actually view a meal they expect to consume.20 In addition, the cephalic salivation response is differential to specific foods. In one study, the greatest salivary increases occurred at the sight of lemon slices and pizza: both of them contain chemical irritants in the form of acids or pungent spices, which are powerful salivary stimulants.21 Emotional input has also been shown to have an effect on the physiology of salivation:22 specifically, emotional stress reduces salivation, whereas relaxation enhances it.23 Theoretically, using specific suggestions for relaxation combined with imagining food and/or environments which are known to encourage salivation may have a beneficial
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effect on salivation. We, therefore, conducted this prospective pilot study to assess the effectiveness of hypnosis in the treatment of xerostomia in patients following radiotherapy for head and neck cancer.
Methods Study Approval, Participant Criteria, and Recruitment The protocol and informed consent forms were reviewed and approved by the Institutional Review Board. The study was registered at ClinicalTrials.gov (identifier NCT00408759). Inclusion criteria for this study were the presence of xerostomia following radiotherapy for head and neck cancer ($5000 rad), a lack of response or inability to tolerate pilocarpine, age above 18 years, and the ability to comprehend informed consent. Excluded were patients under the age of 18 years, individuals who received chemotherapy or radiotherapy within the two months preceding the study, inability to complete study questionnaires, use of medications causing dryness of the oral cavity (clonidine, diuretics, and others), chronic hepatitis C infection, human immunodeficiency virus, sarcoidosis, Sjo¨gren’s syndrome, active psychiatric illness, and chronic graft vs. host disease.
Study Protocol Eligible patients received an explanation of the study and its objectives by the referring physician. An in-depth explanation of hypnosis was provided by the study coordinator at the first visit to the medical center where the hypnosis sessions took place. The subjects filled in the visual analog scale (VAS) of a xerostomia questionnaire, and both unstimulated and stimulated whole saliva were collected, as described later. The questionnaires were repeated at one, four, and 12 weeks after treatment, during a meeting with the study coordinator, at which patients also were requested to report any adverse event that may have been related to the study. Baseline unstimulated whole saliva was collected and each participant underwent a formal 30e40-minute session of hypnosis. For a complete description of the hypnosis protocol, see Appendix, published online at www.jpsmjournal.com. Saliva was collected without further stimulation immediately after the hypnosis session.
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The subjects were given a recording of the hypnosis session on a compact disk (CD). They were instructed to listen to it at least twice daily, preferably more, for at least one month, and to complete a hypnosis diary in which they recorded the number of times they actually listened to the CD.
Questionnaires Severity of xerostomia was assessed by two validated questionnaires, the VAS xerostomia questionnaire developed by Pai et al.,24 and a four-item salivary hypofunction questionnaire developed by Fox et al.25 The VAS xerostomia questionnaire has eight items and provides an assessment of various salivary functions, such as dryness of the oral mucosa (lips, mouth, tongue, and throat), and oral function disability, such as difficulty in swallowing and speaking, caused by dryness. There are also two global items on mouth dryness per se, the amount of saliva in mouth and the level of thirst. Subjects were asked to mark their responses to each item on a 10-cm VAS scale of 0 (minimal) to 10 (maximal). According to the literature,26 the primary measure of efficacy in the treatment of xerostomia is an improvement from baseline of at least 2.5 cm in the various domains of the VAS xerostomia questionnaire. The four-item salivary hypofunction questionnaire25 identifies major salivary gland output deficiency or dysfunction. Positive responses to the first three items and a response of ‘‘too little saliva’’ to the fourth are indicative of major salivary gland hypofunction.
Sialometry We chose the whole saliva method (the combined fluid contents of the mouth) from among the many methods for measurement of salivary output (reviewed in detail by Navazesh et al.27). We based our choice considering the diversity of the subjects’ diagnoses and the different anatomical locations of radiation. Whole saliva provides a general assessment of salivary capabilities. According to the literature, the correlation between the amount of saliva collected and the subjective complaints of xerostomia is inconsistent.28 Because we were conducting a pilot study, we were interested to see if improvement in saliva flow following hypnosis could serve as a prognostic factor for efficacy of this intervention.
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The patients who had no response to citric acid stimulation and who presumably had no residual salivary gland function were included to see what, if any, response they would have to hypnosis. In the first visit, whole saliva was collected twice: first for the baseline unstimulated salivary flow rate for which the subjects were asked to expel all saliva produced in five minutes into a preweighted container, and then for the stimulated salivary flow rate for which 2% citric acid was applied on the bilateral dorsolateral tongue surfaces every 15 seconds for one minute, followed by the same five-minute collection period. In the second visit, whole saliva was again taken twice: first for the baseline, unstimulated salivary flow rate and then for the posthypnosis salivary flow rate with the five-minute collection period. The saliva-containing tubes were then weighed. The flow rate was reported in values of mL/minute assuming that a specific gravity of 1.0 equals 1 mL. Data were analyzed using the Mann-Whitney test to compare baseline and posthypnosis results, and correlations were assessed by Spearman’s correlation coefficient.
Results Of a total of 15 patients who fulfilled the criteria of major salivary gland hypofunction, 12 completed the study. After meeting with the
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hypnotist, two patients declined to continue, one from a fear of hypnosis and the other from the strong belief it would not help him. A third patient was excluded from the study by the hypnotist because of extreme lack of attentiveness during the hypnosis interview and the consequent judgment that the patient was not amenable to being hypnotized. This exclusion was based on studies showing strong correlation between hypnotic susceptibility and sustained attention abilities and vice versa.29 Thus, there were complete data for 12 patients, and they comprised the final study group. Table 1 displays the characteristics of the study group.
Overall Changes At one, four, and 12 weeks, six of the 12 patients reported significant improvement in oral dryness and oral function. Eight patients reported a global (overall) improvement in xerostomia symptoms at 12 weeks. Figure 1 shows the participants’ average decline in symptom severity in the three domains of oral dryness, function, and global xerostomia symptoms. The saliva flow rate increased in nine patients following hypnosis, but there was no significant correlation between the magnitude of change in saliva flow rate and changes in subjective measures (r ¼ 0.134). Some of the more impressive responders in subjective measures did not show increase in
Table 1 Patient Characteristics No.
Age
Sex
1 2 3
57 65 76
M M F
4
70
F
5
68
F
6
58
F
7 8
61 31
F M
9 10
46 60
M F
11
41
M
12
53
M
Diagnosis Nasopharyngeal carcinoma Nasopharyngeal carcinoma Squamous cell carcinoma of the alveolar ridge Adenoid cystic carcinoma of the palate Squamous cell carcinoma of the tongue Mucoepidermal carcinoma of the parotid gland Nasopharyngeal carcinoma Esthesioneuroblastoma of the cribriform plate and nasal cavity Nasopharyngeal carcinoma Polymorphous low-grade adenocarcinoma of the parotid gland Poorly differentiated adenocarcinoma of the parotid gland Squamous cell carcinoma of the tongue
Surgical Treatment
Radiation Dose
Years since Radiation
No surgery No surgery Resection and neck dissection
7000 rad 7000 rad 7000 rad
3 1 4
Resection
6000 rad
7
Glossectomy and neck dissection
7000 rad
2
Total parotidectomy
7000 rad
2.5
No surgery Endoscopic excision
7000 rad 6000 rad
1 0.5
Neck dissection Total parotidectomy
7000 rad 7000 rad
6 4
Total parotidectomy and neck dissection Glossectomy and neck dissection
7000 rad
5.5
6000 rad
9
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10
Discussion
Oral Function Oral Dryness Global Xerostomia
9 8 7
In this small, prospective, observational pilot study, we assessed the efficacy of hypnosis to alleviate xerostomia in patients following radiotherapy for head and neck cancer. Eight of 12 patients improved in subjective measures following hypnotherapy. We also observed a positive relation between adherence to treatment recommendations (i.e., frequently listening to the hypnosis CD) and subjective outcomes. We did not observe a direct correlation between the magnitude of change in saliva flow following hypnosis and subjective outcomes. Of note, a lack of salivary response did not predict treatment failure. Because of the small number of participants and lack of control group, these findings should be interpreted cautiously. They call for confirmation in a larger and more rigorous trial. We suggest that hypnosis may influence xerostomia by several mechanisms:
VAS
6 5 4 3 2 1 0
0
1
4
12
Weeks
Fig. 1. Average decline in symptom severity in the three domains of oral dryness, function, and global xerostomia symptoms.
saliva flow rate and vice versa (Fig. 2). No adverse events following hypnosis were reported. Figure 2 shows the correlations between improvements in global xerostomia symptoms, the saliva flow after hypnosis session, and the number of hypnosis sessions. The improvement in global symptoms did not correlate significantly with the increase in saliva flow following hypnosis (Spearman’s correlation coefficient r ¼ 0.134), but there was a significant correlation between the magnitude of improvement in overall symptoms and the amount of exposure to the hypnosis process: patients who listened to the hypnosis CD more often had significantly better outcomes than those who listened less (r ¼ 0.714, P ¼ 0.009).
Counteracting Negative Expectancy. Based on previous experience, patients learn to expect changes in symptoms following suggestions.30 This is often termed a nocebo effect or placebo side effect. Response expectancy may also be relevant to patients receiving radiotherapy to the head and neck. During the process of informed consent, patients are given ‘‘negative’’ suggestions, that is, that radiotherapy will damage their salivary glands and cause dry mouth. It could be reasoned that such negative suggestions may affect certain patients to varying degrees. Hypnosis may ‘‘counteract’’ or ‘‘unwind’’ the negative suggestion,
0.8
300
0.7
250
0.6
200
0.5 0.4
150
0.3
100
0.2
50
0.1
# of Self Hypnosis Sessions
Change From Baseline
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0
0 1
2
3
4
5
6
7
Patient number
Global Improvement at 12 weeks
8
9
10
11
12
Salivary Flow After Hypnosis
Number of Self Hypnosis Sessions
Fig. 2. Correlations between improvement in global xerostomia symptoms, post-hypnosis saliva flow, and number of hypnosis sessions.
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substitute it with a positive one, and lessen the amount of xerostomia. Hypnosis may, thus, limit the effect of radiotherapy on salivary glands to the ‘‘net’’ effect of radiation, without the negative contribution of expectation. Optimizing Physiological Environment for Salivation. Salivation is a complex secretory function, which is modulated by the cortex. Cortical stimulation of salivation increases in a state of relaxation or imagery of food. Hypnosis can induce relaxation by utilizing a wide range of techniques, such as progressive muscular relaxation or imagining pleasant and calming environments. Imagery of food, especially food that triggers salivation in healthy individuals, can be achieved by using appropriate hypnotic suggestions. Imagery of an activity induced by hypnosis has been shown to trigger cortical activity, simulating that which is observed in real activity.31 In addition, upon repetition of food imagery and relaxation exercise, the salivary response may be intensified, similar to a ‘‘Pavlovian’’ conditioned response to specific cues. Thus, repetition of relaxation and saliva triggering imagery optimizes the physiological environment for salivation.
Study Limitations The major limitations of this trial are its small sample size, absence of a control group, and lack of patient blinding. Thus, the outcomes of this study could be either because of regression to the mean phenomena or placebo effect, respectively, and, therefore, must be interpreted accordingly. Other limitations are the lack of overall quality of life assessment before and after treatment and the need for a longer follow-up to assess the long-term effect of hypnosis on xerostomia.
Areas for Future Research Future studies should attempt to address issues, such as whether predictors of treatment efficacy exist, for example, hypnotizability, response to citric acid/hypnosis stimulation, or a priori expectations from hypnosis. Outcomes of different sets of hypnotic suggestions and styles should be compared for efficacy. In addition, whether hypnosis has an added value over the nonspecific effects of attention,
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should be teased out using an attention control group. In conclusion, our preliminary data showing possible benefit of hypnosis for xerostomia that had been induced by radiotherapy for head and neck cancer call for larger confirmatory studies.
Acknowledgments The authors thank Mr. Joseph Meyerson for his assistance in developing the hypnosis protocol, and Dr. Ada Tamir and Mr. Jacob Schiff for the statistical analysis.
References 1. Forastiere A, Koch W, Trotti A, et al. Head and neck cancer. N Engl J Med 2001;345:1890e1900. 2. Li Y, Taylor JM, Ten Haken RK, et al. The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 2007;67:660e669. 3. Sreebny LM. Xerostomia: diagnosis, management and clinical complications. In: Edgar WM, O’Mullane DM, eds. Saliva and oral health. London: British Dental Association, 1996: 43e66. 4. Dirix P, Nuyts S, Van den Bogaert W. Radiation-induced xerostomia in patients with head and neck cancer: a literature review. Cancer 2006;107: 2525e2534. 5. Seikaly H, Jha N, Harris JR, et al. Long-term outcomes of submandibular gland transfer for prevention of postradiation xerostomia. Arch Otolaryngol Head Neck Surg 2004;130:956e961. 6. Johnstone PA, Peng YP, May BC, et al. Acupuncture for pilocarpine-resistant xerostomia following radiotherapy for head and neck malignancies. Int J Radiat Oncol Biol Phys 2001;50:353e357. 7. Wong RK, Jones GW, Sagar SM, et al. A phase I-II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy. Int J Radiat Oncol Biol Phys 2003;57:472e480. 8. Dirix P, Nuyts S, Vander Poorten V, et al. The influence of xerostomia after radiotherapy on quality of life: results of a questionnaire in head and neck cancer. Support Care Cancer 2008;16: 171e179. 9. Green JP, Barabasz AF, Barrett D, et al. Forging ahead: the 2003 APA Division 30 definition of hypnosis. J Clin Exp Hypn 2005;53:259e264. 10. Kihlstrom JF. Hypn Ann Rev Psychol 1985;36: 385e418.
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11. Kirsch I, Lynn SJ. The altered state of hypnosis: changes in the theoretical landscape. Am Psychol 1995;50:846e858. 12. Kirsch I, Montgomery G, Sapirstein G. Hypnosis as an adjunct to cognitive-behavioral psychotherapy: a meta-analysis. J Consult Clin Psychol 1995;63: 214e220. 13. Cardena E, Spiegel D. Suggestibility, absorption and dissociation: an integrative model of hypnosis. In: Schumaker JF, ed. Human suggestibility: advances in theory, research, and application. New York: Routledge, 1991: 93e107. 14. Schumaker JF. Human suggestibility: advances in theory, research, and application. New York: Routledge, 1991. 15. Wolberg LR. Medical hypnosis. In: The principles of hypnotherapy, vol. 1. New York: Grune & Stratton, 1948. 16. Sterman MB, Kaiser DA, Veigel B. Spectral analysis of event-related EEG responses during short-term memory performance. Brain Topogr 1996;9:21e30. 17. Maquet P, Faymonville ME, Degueldre C, et al. Functional neuroanatomy of hypnotic state. Biol Psychiatry 1999;45:327e333. 18. Pavlov IP. Conditioned reflexes. New York: Dover Publications, 1927. 19. Wooley OW, Wooley SC, Dunham RB. Deprivation, expectation and threat: effects on salivation in the obese and nonobese. Physiol Behav 1976; 17:187e193.
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22. Garrett JR. The proper role of nerves in salivary secretion: a review. J Dent Res 1987;66:387e397. 23. Morse DR. Stress, relaxation and saliva: a follow-up study involving clinical endodontic patients. J Human Stress 1981;7:19e26. 24. Pai S, Ghezzi EM, Ship J. Development of a Visual Analogue Scale questionnaire for subjective assessment of salivary function. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91: 311e316. 25. Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomia and objective measures of salivary gland performance. J Am Dent Assoc 1987;115: 581e584. 26. Johnson JT, Ferretti GA, Nethery WJ, et al. Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer. N Engl J Med 1993;329:390e395. 27. Navazesh M, Christensen C, Brightman V. Clinical criteria for the diagnosis of salivary gland hypofunction. J Dent Res 1992;71:1363e1369. 28. LeVeque FG, Montgomery M, Potter D, et al. A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients. J Clin Oncol 1993; 11:1124e1131. 29. Crawford HJ, Brown AM, Moon CE. Sustained attentional and disattentional abilities: differences between low and highly hypnotizable persons. J Abnorm Psychol 1993;102:534e543.
20. Wooley SC, Wooley OW. Salivation to the sight and thought of food: a new measure of appetite. Psychosom Med 1973;35:136e142.
30. Put C, Van den Bergh O, Van Ongeval E, et al. Negative affectivity and the influence of suggestion on asthma symptoms. J Psychosom Res 2004;57: 249e255.
21. Christensen CM, Navazesh M. Anticipatory salivary flow to the sight of different foods. Appetite 1984;5:307e315.
31. Faymonville ME, Laureys S, Degueldre C, et al. Neural mechanisms of antinociceptive effects of hypnosis. Anesthesiology 2000;92:1257e1267.
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Appendix Hypnosis Protocol The hypnosis protocol was developed by our group following consultation with leading hypnotherapists in Israel. Each subject was interviewed by the study hypnotist to establish rapport and to retrieve information with possible usefulness for hypnosis, such as favorite foods and settings that he/she considered conducive to relaxing, especially those associated with flowing water (e.g., waterfall, creeks, and others). A 30e40-minute hypnosis session would then begin in the following sequence: a. Induction. Induction of hypnosis was achieved using either progressive muscle relaxation, eye fixation, or breathing techniques. b. Deepening. When the subject appeared to be relaxed, the hypnotist used suggestion to reach a deeper trance state: ‘‘.and when I count from five to one you will feel yourself going deeper and deeper into a state of relaxation..’’ c. Suggestions. The subjects’ personal information obtained in the interviews was adapted for hypnotic suggestions. They were guided to imagine a scene, such as preparation of their favorite food: ‘‘.and now imagine yourself in your kitchen,. you may notice the smell of fried onions and garlic while your favorite dish is being cooked.you remember how in the past you enjoyed the taste of this dish.you may recall how your mouth used to water in response to the delicious taste.as you remember the wonderful taste of the dish you may be surprised to notice how your mouth is watering..’’ The subjects were then given a second suggestion associated with the choice of setting they considered as being relaxing. For example, ‘‘Imagine yourself near a waterfall and reaching out to scoop sips of refreshing cool water..’’ The third suggestion was to imagining themselves picking a juicy ripe lemon from a lemon tree: ‘‘.you are now cutting a slice of lemon and squirting the sour juice into your mouth.your mouth fills with saliva..’’ During the session, the hypnotist observed the subject for signs of increased salivation, such as swallowing, mouth and tongue
movements, and others. The suggestion that had triggered the most salivation was then repeated and intensified. Then, the subject received instructions for controlling salivation. This is termed an ‘‘anchoring technique,’’ which creates the association of salivation with a specific reproducible gesture: ‘‘.imagine a ‘volume knob,’ like a volume knob on your radio, with your fingers amplifying or decreasing the volume.you may be surprised to observe how you control salivation in the same manner..’’ After practicing control of the volume knob, a couple of general well-being and ego-strengthening suggestions were given: ‘‘. as you continue to observe yourself gaining control of your salivation, your control over your general health and well-being will improve, too..’’ d. Future projection. The subjects were told ‘‘.and you may see yourself in a few months from now, your mouth has the perfect level of moisture.you do not have any need for water bottles.your sleep and speech are normal.and when you look back you notice how easy it was to achieve all this..’’ e. Dehypnotization. The subjects were guided to gradually return into a wakeful and refreshed state: ‘‘.when I count up from one to five you will gradually go into a wakeful and refreshed state..’’ The hypnotist and the subjects then discussed the experience in the hypnosis session to reinforce their confidence in their ability to control salivation. The subjects were given a CD with a recording of their hypnosis session and instructed to listen to the CD at least twice daily for at least one month.
Journal of Pain and Symptom Management
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Clinical Note
Hypnosis for Postradiation Xerostomia in Head and Neck Cancer Patients: A Pilot Study Elad Schiff, MD, Jorge G. Mogilner, MD, Eyal Sella, MD, Ilana Doweck, MD, Oded Hershko, MD, Eran Ben-Arye, MD, and Noam Yarom, MD Department of Internal Medicine (E.S.), Bnai Zion Medical Center, Haifa; Department for Complementary/Integrative Medicine, Law and Ethics (E.S.), and The International Center for Health, Law and Ethics (E.S.), Haifa University, Haifa; Department of Pediatric Surgery (J.G.M.), The Ruth & Bruce Rappaport Faculty of Medicine, and the Complementary and Traditional Medicine Unit (E.B.-A.), Department of Family Medicine, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa; Department of Otolaryngology-Head and Neck Surgery (E.S., I.D.), Carmel Medical Center, Haifa, Israel; Faculty of Medicine (O.H.), Semmelweis University, Budapest, Hungary; Clalit Health Services (E.B.-A.), Haifa and Western Galilee District; and Oral Medicine Clinic (N.Y.), Department of Oral and Maxillofacial Surgery, Sheba Medical Center, Tel-Hashomer, Israel
Abstract Xerostomia, the sensation of dry mouth, affects almost all patients who undergo radiotherapy for cancer in the head and neck area. Current therapies for xerostomia are inadequate, and the condition negatively impacts the quality of life. This prospective observational pilot study aimed to evaluate whether hypnosis could improve salivation and decrease xerostomia. Twelve patients with xerostomia after radiotherapy for head and neck cancer were assessed for severity of xerostomia symptoms and sialometry. They then received a single hypnosis session with specific suggestions to increase salivation. The session was recorded on a compact disk (CD), and the participants were instructed to listen to it twice a day for one month. Sialometry was repeated immediately after hypnosis. Validated xerostomia questionnaires were completed at one, four, and 12 weeks after hypnosis. A substantial overall improvement was reported by eight patients at 12 weeks (66%). The saliva flow rate increased on sialometry in nine patients following hypnosis (75%). There was no correlation between the magnitude of changes in the measured saliva flow rate and changes in subjective measures (Spearman’s correlation coefficient r ¼ 0.134). Symptomatic improvement significantly correlated with the number of times the patients listened to the hypnosis CD (r ¼ 0.714, P ¼ 0.009). No adverse events were reported. The data from this small observational trial suggest that hypnosis may be an effective treatment for xerostomia. Confirmation in a larger randomized and controlled investigation is warranted. J Pain Symptom Manage 2009;37:1086e1092. Ó 2009 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Keywords Xerostomia, dry mouth, radiation, salivation, hypnosis
Dr. Elad Schiff and Dr. Jorge G. Mogilner contributed equally to the study. Address correspondence to: Elad Schiff, MD, Department of Internal Medicine B, Bnai Zion Medical Ó 2009 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved.
Center, P.O. Box 4940, Haifa 31048, Israel. E-mail: [email protected] Accepted for publication: July 25, 2008.
0885-3924/09/$esee front matter doi:10.1016/j.jpainsymman.2008.07.005
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Hypnosis for Postradiation Xerostomia in Head and Neck Cancer
Introduction Each year, approximately 43,000 people are diagnosed with head and neck cancer in the United States.1 Many patients receive radiation therapy delivered to the head and neck area, which results in injury to salivary glands, eventually leading to little or no saliva production. The amount of salivary flow reduction depends on the radiation dose and fractional size, as well as the volume of salivary glands irradiated.2 Up to 100% of patients receiving radical radiotherapy develop some degree of xerostomia, the subjective sensation of dryness of the mouth. They also may have oral discomfort and pain, greatly increased susceptibility to dental caries, frequent oral infections, and difficulty in speaking, chewing, and swallowing. These outcomes can lead to severe oral disease, nutritional deficiencies, and an overall decline in quality of life.3 There are few treatment options for alleviating xerostomia in these patients. Salivary substitutes and sialogogues, such as pilocarpine,4 are often tried. Submandibular gland transfer,5 acupuncture,6 and acupuncture-like transcutaneous nerve stimulation7 have been suggested. These treatment modalities have shown various degrees of effectiveness and diverse side effects. Xerostomia continues to have a substantial negative impact on the quality of life of survivors of head and neck cancer.8 Medical hypnosis is the clinical application of hypnosis to medical disorders and procedures. As defined by the American Psychological Association, a hypnotic procedure is used to encourage and evaluate responses to suggestions.9 Kihlstrom described hypnosis as ‘‘a set of procedures in which a person designated as the hypnotherapist suggests that another person (the patient or subject) experience various changes in sensation, perception, cognition, or control over behavior.’’10 Others, such as Kirsch and Lynn,11 described hypnosis as simply ‘‘a heightened state of relaxation or a state of focused attention.’’ More recently, hypnosis has been conceptualized as a set of behavioral techniques.12 A hypnotic session usually has an induction phase and an application phase. During the induction phase, the individual begins to enter a hypnotic state, during which there are few competing cognitive demands and less self-
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reflective thought.13 This allows suggestibility, which is defined as ‘‘communication that is accepted uncritically.’’14 During the application phase, specific suggestions are provided according to the treatment goals. Logistically, hypnosis is done in live sessions with a hypnotherapist facilitating the process. Another commonly used technique is teaching self-hypnosis at a formal session with a hypnotherapist, during which individuals learn how to enter the hypnotic state on their own. To achieve the latter goal, sessions are often recorded for regular practice at the client’s home.15 Whether facilitated by a hypnotherapist or carried out by the subjects themselves, it is generally agreed that all hypnosis is, in fact, selfhypnosis. Several mechanisms have been suggested to explain how hypnosis exerts its effects. Electroencephalographic studies of hypnotic states show very slow high-range theta waves (5e7 Hz), which are typically associated with loss of executive control and reflect massive cortical inhibition.16 On the other hand, when the hypnotic state involves specific stimulatory sensory or motor suggestions, the relevant sensory and motor areas of the brain may be activated even more than they are during nonhypnotic conditions.17 Salivation can be conditioned, as described in the classic studies by Pavlov.18 Seeing certain foods or just thinking about food can trigger salivation in an expectant manner.19 The anticipation of food, which constitutes the cephalic phase of alimentary secretions, has an effect on the magnitude of salivation. Subjects will demonstrate more salivation when they actually view a meal they expect to consume.20 In addition, the cephalic salivation response is differential to specific foods. In one study, the greatest salivary increases occurred at the sight of lemon slices and pizza: both of them contain chemical irritants in the form of acids or pungent spices, which are powerful salivary stimulants.21 Emotional input has also been shown to have an effect on the physiology of salivation:22 specifically, emotional stress reduces salivation, whereas relaxation enhances it.23 Theoretically, using specific suggestions for relaxation combined with imagining food and/or environments which are known to encourage salivation may have a beneficial
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effect on salivation. We, therefore, conducted this prospective pilot study to assess the effectiveness of hypnosis in the treatment of xerostomia in patients following radiotherapy for head and neck cancer.
Methods Study Approval, Participant Criteria, and Recruitment The protocol and informed consent forms were reviewed and approved by the Institutional Review Board. The study was registered at ClinicalTrials.gov (identifier NCT00408759). Inclusion criteria for this study were the presence of xerostomia following radiotherapy for head and neck cancer ($5000 rad), a lack of response or inability to tolerate pilocarpine, age above 18 years, and the ability to comprehend informed consent. Excluded were patients under the age of 18 years, individuals who received chemotherapy or radiotherapy within the two months preceding the study, inability to complete study questionnaires, use of medications causing dryness of the oral cavity (clonidine, diuretics, and others), chronic hepatitis C infection, human immunodeficiency virus, sarcoidosis, Sjo¨gren’s syndrome, active psychiatric illness, and chronic graft vs. host disease.
Study Protocol Eligible patients received an explanation of the study and its objectives by the referring physician. An in-depth explanation of hypnosis was provided by the study coordinator at the first visit to the medical center where the hypnosis sessions took place. The subjects filled in the visual analog scale (VAS) of a xerostomia questionnaire, and both unstimulated and stimulated whole saliva were collected, as described later. The questionnaires were repeated at one, four, and 12 weeks after treatment, during a meeting with the study coordinator, at which patients also were requested to report any adverse event that may have been related to the study. Baseline unstimulated whole saliva was collected and each participant underwent a formal 30e40-minute session of hypnosis. For a complete description of the hypnosis protocol, see Appendix, published online at www.jpsmjournal.com. Saliva was collected without further stimulation immediately after the hypnosis session.
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The subjects were given a recording of the hypnosis session on a compact disk (CD). They were instructed to listen to it at least twice daily, preferably more, for at least one month, and to complete a hypnosis diary in which they recorded the number of times they actually listened to the CD.
Questionnaires Severity of xerostomia was assessed by two validated questionnaires, the VAS xerostomia questionnaire developed by Pai et al.,24 and a four-item salivary hypofunction questionnaire developed by Fox et al.25 The VAS xerostomia questionnaire has eight items and provides an assessment of various salivary functions, such as dryness of the oral mucosa (lips, mouth, tongue, and throat), and oral function disability, such as difficulty in swallowing and speaking, caused by dryness. There are also two global items on mouth dryness per se, the amount of saliva in mouth and the level of thirst. Subjects were asked to mark their responses to each item on a 10-cm VAS scale of 0 (minimal) to 10 (maximal). According to the literature,26 the primary measure of efficacy in the treatment of xerostomia is an improvement from baseline of at least 2.5 cm in the various domains of the VAS xerostomia questionnaire. The four-item salivary hypofunction questionnaire25 identifies major salivary gland output deficiency or dysfunction. Positive responses to the first three items and a response of ‘‘too little saliva’’ to the fourth are indicative of major salivary gland hypofunction.
Sialometry We chose the whole saliva method (the combined fluid contents of the mouth) from among the many methods for measurement of salivary output (reviewed in detail by Navazesh et al.27). We based our choice considering the diversity of the subjects’ diagnoses and the different anatomical locations of radiation. Whole saliva provides a general assessment of salivary capabilities. According to the literature, the correlation between the amount of saliva collected and the subjective complaints of xerostomia is inconsistent.28 Because we were conducting a pilot study, we were interested to see if improvement in saliva flow following hypnosis could serve as a prognostic factor for efficacy of this intervention.
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Hypnosis for Postradiation Xerostomia in Head and Neck Cancer
The patients who had no response to citric acid stimulation and who presumably had no residual salivary gland function were included to see what, if any, response they would have to hypnosis. In the first visit, whole saliva was collected twice: first for the baseline unstimulated salivary flow rate for which the subjects were asked to expel all saliva produced in five minutes into a preweighted container, and then for the stimulated salivary flow rate for which 2% citric acid was applied on the bilateral dorsolateral tongue surfaces every 15 seconds for one minute, followed by the same five-minute collection period. In the second visit, whole saliva was again taken twice: first for the baseline, unstimulated salivary flow rate and then for the posthypnosis salivary flow rate with the five-minute collection period. The saliva-containing tubes were then weighed. The flow rate was reported in values of mL/minute assuming that a specific gravity of 1.0 equals 1 mL. Data were analyzed using the Mann-Whitney test to compare baseline and posthypnosis results, and correlations were assessed by Spearman’s correlation coefficient.
Results Of a total of 15 patients who fulfilled the criteria of major salivary gland hypofunction, 12 completed the study. After meeting with the
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hypnotist, two patients declined to continue, one from a fear of hypnosis and the other from the strong belief it would not help him. A third patient was excluded from the study by the hypnotist because of extreme lack of attentiveness during the hypnosis interview and the consequent judgment that the patient was not amenable to being hypnotized. This exclusion was based on studies showing strong correlation between hypnotic susceptibility and sustained attention abilities and vice versa.29 Thus, there were complete data for 12 patients, and they comprised the final study group. Table 1 displays the characteristics of the study group.
Overall Changes At one, four, and 12 weeks, six of the 12 patients reported significant improvement in oral dryness and oral function. Eight patients reported a global (overall) improvement in xerostomia symptoms at 12 weeks. Figure 1 shows the participants’ average decline in symptom severity in the three domains of oral dryness, function, and global xerostomia symptoms. The saliva flow rate increased in nine patients following hypnosis, but there was no significant correlation between the magnitude of change in saliva flow rate and changes in subjective measures (r ¼ 0.134). Some of the more impressive responders in subjective measures did not show increase in
Table 1 Patient Characteristics No.
Age
Sex
1 2 3
57 65 76
M M F
4
70
F
5
68
F
6
58
F
7 8
61 31
F M
9 10
46 60
M F
11
41
M
12
53
M
Diagnosis Nasopharyngeal carcinoma Nasopharyngeal carcinoma Squamous cell carcinoma of the alveolar ridge Adenoid cystic carcinoma of the palate Squamous cell carcinoma of the tongue Mucoepidermal carcinoma of the parotid gland Nasopharyngeal carcinoma Esthesioneuroblastoma of the cribriform plate and nasal cavity Nasopharyngeal carcinoma Polymorphous low-grade adenocarcinoma of the parotid gland Poorly differentiated adenocarcinoma of the parotid gland Squamous cell carcinoma of the tongue
Surgical Treatment
Radiation Dose
Years since Radiation
No surgery No surgery Resection and neck dissection
7000 rad 7000 rad 7000 rad
3 1 4
Resection
6000 rad
7
Glossectomy and neck dissection
7000 rad
2
Total parotidectomy
7000 rad
2.5
No surgery Endoscopic excision
7000 rad 6000 rad
1 0.5
Neck dissection Total parotidectomy
7000 rad 7000 rad
6 4
Total parotidectomy and neck dissection Glossectomy and neck dissection
7000 rad
5.5
6000 rad
9
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Discussion
Oral Function Oral Dryness Global Xerostomia
9 8 7
In this small, prospective, observational pilot study, we assessed the efficacy of hypnosis to alleviate xerostomia in patients following radiotherapy for head and neck cancer. Eight of 12 patients improved in subjective measures following hypnotherapy. We also observed a positive relation between adherence to treatment recommendations (i.e., frequently listening to the hypnosis CD) and subjective outcomes. We did not observe a direct correlation between the magnitude of change in saliva flow following hypnosis and subjective outcomes. Of note, a lack of salivary response did not predict treatment failure. Because of the small number of participants and lack of control group, these findings should be interpreted cautiously. They call for confirmation in a larger and more rigorous trial. We suggest that hypnosis may influence xerostomia by several mechanisms:
VAS
6 5 4 3 2 1 0
0
1
4
12
Weeks
Fig. 1. Average decline in symptom severity in the three domains of oral dryness, function, and global xerostomia symptoms.
saliva flow rate and vice versa (Fig. 2). No adverse events following hypnosis were reported. Figure 2 shows the correlations between improvements in global xerostomia symptoms, the saliva flow after hypnosis session, and the number of hypnosis sessions. The improvement in global symptoms did not correlate significantly with the increase in saliva flow following hypnosis (Spearman’s correlation coefficient r ¼ 0.134), but there was a significant correlation between the magnitude of improvement in overall symptoms and the amount of exposure to the hypnosis process: patients who listened to the hypnosis CD more often had significantly better outcomes than those who listened less (r ¼ 0.714, P ¼ 0.009).
Counteracting Negative Expectancy. Based on previous experience, patients learn to expect changes in symptoms following suggestions.30 This is often termed a nocebo effect or placebo side effect. Response expectancy may also be relevant to patients receiving radiotherapy to the head and neck. During the process of informed consent, patients are given ‘‘negative’’ suggestions, that is, that radiotherapy will damage their salivary glands and cause dry mouth. It could be reasoned that such negative suggestions may affect certain patients to varying degrees. Hypnosis may ‘‘counteract’’ or ‘‘unwind’’ the negative suggestion,
0.8
300
0.7
250
0.6
200
0.5 0.4
150
0.3
100
0.2
50
0.1
# of Self Hypnosis Sessions
Change From Baseline
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0
0 1
2
3
4
5
6
7
Patient number
Global Improvement at 12 weeks
8
9
10
11
12
Salivary Flow After Hypnosis
Number of Self Hypnosis Sessions
Fig. 2. Correlations between improvement in global xerostomia symptoms, post-hypnosis saliva flow, and number of hypnosis sessions.
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Hypnosis for Postradiation Xerostomia in Head and Neck Cancer
substitute it with a positive one, and lessen the amount of xerostomia. Hypnosis may, thus, limit the effect of radiotherapy on salivary glands to the ‘‘net’’ effect of radiation, without the negative contribution of expectation. Optimizing Physiological Environment for Salivation. Salivation is a complex secretory function, which is modulated by the cortex. Cortical stimulation of salivation increases in a state of relaxation or imagery of food. Hypnosis can induce relaxation by utilizing a wide range of techniques, such as progressive muscular relaxation or imagining pleasant and calming environments. Imagery of food, especially food that triggers salivation in healthy individuals, can be achieved by using appropriate hypnotic suggestions. Imagery of an activity induced by hypnosis has been shown to trigger cortical activity, simulating that which is observed in real activity.31 In addition, upon repetition of food imagery and relaxation exercise, the salivary response may be intensified, similar to a ‘‘Pavlovian’’ conditioned response to specific cues. Thus, repetition of relaxation and saliva triggering imagery optimizes the physiological environment for salivation.
Study Limitations The major limitations of this trial are its small sample size, absence of a control group, and lack of patient blinding. Thus, the outcomes of this study could be either because of regression to the mean phenomena or placebo effect, respectively, and, therefore, must be interpreted accordingly. Other limitations are the lack of overall quality of life assessment before and after treatment and the need for a longer follow-up to assess the long-term effect of hypnosis on xerostomia.
Areas for Future Research Future studies should attempt to address issues, such as whether predictors of treatment efficacy exist, for example, hypnotizability, response to citric acid/hypnosis stimulation, or a priori expectations from hypnosis. Outcomes of different sets of hypnotic suggestions and styles should be compared for efficacy. In addition, whether hypnosis has an added value over the nonspecific effects of attention,
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should be teased out using an attention control group. In conclusion, our preliminary data showing possible benefit of hypnosis for xerostomia that had been induced by radiotherapy for head and neck cancer call for larger confirmatory studies.
Acknowledgments The authors thank Mr. Joseph Meyerson for his assistance in developing the hypnosis protocol, and Dr. Ada Tamir and Mr. Jacob Schiff for the statistical analysis.
References 1. Forastiere A, Koch W, Trotti A, et al. Head and neck cancer. N Engl J Med 2001;345:1890e1900. 2. Li Y, Taylor JM, Ten Haken RK, et al. The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 2007;67:660e669. 3. Sreebny LM. Xerostomia: diagnosis, management and clinical complications. In: Edgar WM, O’Mullane DM, eds. Saliva and oral health. London: British Dental Association, 1996: 43e66. 4. Dirix P, Nuyts S, Van den Bogaert W. Radiation-induced xerostomia in patients with head and neck cancer: a literature review. Cancer 2006;107: 2525e2534. 5. Seikaly H, Jha N, Harris JR, et al. Long-term outcomes of submandibular gland transfer for prevention of postradiation xerostomia. Arch Otolaryngol Head Neck Surg 2004;130:956e961. 6. Johnstone PA, Peng YP, May BC, et al. Acupuncture for pilocarpine-resistant xerostomia following radiotherapy for head and neck malignancies. Int J Radiat Oncol Biol Phys 2001;50:353e357. 7. Wong RK, Jones GW, Sagar SM, et al. A phase I-II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy. Int J Radiat Oncol Biol Phys 2003;57:472e480. 8. Dirix P, Nuyts S, Vander Poorten V, et al. The influence of xerostomia after radiotherapy on quality of life: results of a questionnaire in head and neck cancer. Support Care Cancer 2008;16: 171e179. 9. Green JP, Barabasz AF, Barrett D, et al. Forging ahead: the 2003 APA Division 30 definition of hypnosis. J Clin Exp Hypn 2005;53:259e264. 10. Kihlstrom JF. Hypn Ann Rev Psychol 1985;36: 385e418.
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11. Kirsch I, Lynn SJ. The altered state of hypnosis: changes in the theoretical landscape. Am Psychol 1995;50:846e858. 12. Kirsch I, Montgomery G, Sapirstein G. Hypnosis as an adjunct to cognitive-behavioral psychotherapy: a meta-analysis. J Consult Clin Psychol 1995;63: 214e220. 13. Cardena E, Spiegel D. Suggestibility, absorption and dissociation: an integrative model of hypnosis. In: Schumaker JF, ed. Human suggestibility: advances in theory, research, and application. New York: Routledge, 1991: 93e107. 14. Schumaker JF. Human suggestibility: advances in theory, research, and application. New York: Routledge, 1991. 15. Wolberg LR. Medical hypnosis. In: The principles of hypnotherapy, vol. 1. New York: Grune & Stratton, 1948. 16. Sterman MB, Kaiser DA, Veigel B. Spectral analysis of event-related EEG responses during short-term memory performance. Brain Topogr 1996;9:21e30. 17. Maquet P, Faymonville ME, Degueldre C, et al. Functional neuroanatomy of hypnotic state. Biol Psychiatry 1999;45:327e333. 18. Pavlov IP. Conditioned reflexes. New York: Dover Publications, 1927. 19. Wooley OW, Wooley SC, Dunham RB. Deprivation, expectation and threat: effects on salivation in the obese and nonobese. Physiol Behav 1976; 17:187e193.
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22. Garrett JR. The proper role of nerves in salivary secretion: a review. J Dent Res 1987;66:387e397. 23. Morse DR. Stress, relaxation and saliva: a follow-up study involving clinical endodontic patients. J Human Stress 1981;7:19e26. 24. Pai S, Ghezzi EM, Ship J. Development of a Visual Analogue Scale questionnaire for subjective assessment of salivary function. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91: 311e316. 25. Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomia and objective measures of salivary gland performance. J Am Dent Assoc 1987;115: 581e584. 26. Johnson JT, Ferretti GA, Nethery WJ, et al. Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer. N Engl J Med 1993;329:390e395. 27. Navazesh M, Christensen C, Brightman V. Clinical criteria for the diagnosis of salivary gland hypofunction. J Dent Res 1992;71:1363e1369. 28. LeVeque FG, Montgomery M, Potter D, et al. A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients. J Clin Oncol 1993; 11:1124e1131. 29. Crawford HJ, Brown AM, Moon CE. Sustained attentional and disattentional abilities: differences between low and highly hypnotizable persons. J Abnorm Psychol 1993;102:534e543.
20. Wooley SC, Wooley OW. Salivation to the sight and thought of food: a new measure of appetite. Psychosom Med 1973;35:136e142.
30. Put C, Van den Bergh O, Van Ongeval E, et al. Negative affectivity and the influence of suggestion on asthma symptoms. J Psychosom Res 2004;57: 249e255.
21. Christensen CM, Navazesh M. Anticipatory salivary flow to the sight of different foods. Appetite 1984;5:307e315.
31. Faymonville ME, Laureys S, Degueldre C, et al. Neural mechanisms of antinociceptive effects of hypnosis. Anesthesiology 2000;92:1257e1267.
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Appendix Hypnosis Protocol The hypnosis protocol was developed by our group following consultation with leading hypnotherapists in Israel. Each subject was interviewed by the study hypnotist to establish rapport and to retrieve information with possible usefulness for hypnosis, such as favorite foods and settings that he/she considered conducive to relaxing, especially those associated with flowing water (e.g., waterfall, creeks, and others). A 30e40-minute hypnosis session would then begin in the following sequence: a. Induction. Induction of hypnosis was achieved using either progressive muscle relaxation, eye fixation, or breathing techniques. b. Deepening. When the subject appeared to be relaxed, the hypnotist used suggestion to reach a deeper trance state: ‘‘.and when I count from five to one you will feel yourself going deeper and deeper into a state of relaxation..’’ c. Suggestions. The subjects’ personal information obtained in the interviews was adapted for hypnotic suggestions. They were guided to imagine a scene, such as preparation of their favorite food: ‘‘.and now imagine yourself in your kitchen,. you may notice the smell of fried onions and garlic while your favorite dish is being cooked.you remember how in the past you enjoyed the taste of this dish.you may recall how your mouth used to water in response to the delicious taste.as you remember the wonderful taste of the dish you may be surprised to notice how your mouth is watering..’’ The subjects were then given a second suggestion associated with the choice of setting they considered as being relaxing. For example, ‘‘Imagine yourself near a waterfall and reaching out to scoop sips of refreshing cool water..’’ The third suggestion was to imagining themselves picking a juicy ripe lemon from a lemon tree: ‘‘.you are now cutting a slice of lemon and squirting the sour juice into your mouth.your mouth fills with saliva..’’ During the session, the hypnotist observed the subject for signs of increased salivation, such as swallowing, mouth and tongue
movements, and others. The suggestion that had triggered the most salivation was then repeated and intensified. Then, the subject received instructions for controlling salivation. This is termed an ‘‘anchoring technique,’’ which creates the association of salivation with a specific reproducible gesture: ‘‘.imagine a ‘volume knob,’ like a volume knob on your radio, with your fingers amplifying or decreasing the volume.you may be surprised to observe how you control salivation in the same manner..’’ After practicing control of the volume knob, a couple of general well-being and ego-strengthening suggestions were given: ‘‘. as you continue to observe yourself gaining control of your salivation, your control over your general health and well-being will improve, too..’’ d. Future projection. The subjects were told ‘‘.and you may see yourself in a few months from now, your mouth has the perfect level of moisture.you do not have any need for water bottles.your sleep and speech are normal.and when you look back you notice how easy it was to achieve all this..’’ e. Dehypnotization. The subjects were guided to gradually return into a wakeful and refreshed state: ‘‘.when I count up from one to five you will gradually go into a wakeful and refreshed state..’’ The hypnotist and the subjects then discussed the experience in the hypnosis session to reinforce their confidence in their ability to control salivation. The subjects were given a CD with a recording of their hypnosis session and instructed to listen to the CD at least twice daily for at least one month.