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Stimulus control of anticipatory nausea in cancer chemotherapy
STIMULUS
CONTROL
PAUL
OF ANTICIPATORY CHEMOTHERAPY G. GREENE
and RICHARD
NAUSEA
IN CANCER
J. SEIME
Department
of BehavioralMedicine
Summary manipulation old female conditioned anticipatory maintained
A single subject ABA design was used to evaluate the effect of a stimulus on anticipatory nausea. A lemon soIut1on was orally administered to a hl-yearoncology patient in order to mask taste sensations thought to function as a stimulus eliciting anticipatory symptoms durin g chemotherapy. A decrease in symptoms was observed with the introduction of the taste masking agent and was following withdrawal of the agent.
and Psychiatry.
West Virginia
Universir)-
b1edica.l Center
manipulations might be effective in the management of anticipatory nausea and vomiting. Manipulations that disrupt the predictive relationship between the conditioned stimulus and the unconditioned stimulus should allow the conditioned nausea to extinguish. It should also be possible to eliminate anticipatory nausea and vor_niting by removing or significantly altering the stimuli assumed to elicit the conditioned response. Taste sensations experienced during drug injection have been associated with the development of anticipatory nausea (Nerenz et al., 1982) and may in fact act as conditioned stimuli capable of eliciting it. The following case study represents the use of a masking stimulus to obscure taste sensations thought to function as a conditioned stimulus eliciting anticipatory nausea and gagging behavior.
The emetic potential of antineoplastic agents used in the treatment of cancer has been well documented (Borison and McCarthy, 19S3; Laszlo, 1983). Nausea and vomiting induced by these drugs begins approximately one or two hours after injection and can persist for as long as 24 hours (Moertel and Reimeier, 1969). After receiving several chemotherapy treatments, many patients begin to experience these side effects even before the drugs are administered. Anticipatory nausea and vomiting has been described as a conditioned response (Morrow, 1982; Neese, et al., 1980; Redd and Andersen, 1981). Initially, nausea and vomiting (unconditioned response) are automatically elicited by the antineoplastic agent (unconditioned stimulus). Cues in the environment that reliably predict the administration of chemotherapy gradually become conditioned stimuli capable of eliciting a conditioned response (anticipatory nausea and vomiting). On the basis of this conditioning model, relaxation has been used as a learned response that is incompatible with nausea and vomiting and capable of reducing the severity of these symptoms (Morrow and Morrell, 1982). The conditioning model also suggests that stimulus
CASE
HISTORY
Presenting problem The patient, Sandra, a 61-year-old Caucasian female. was initially diagnosed with intraductal breast cancer in 1979. At that time, she underwent a right modified radical mastectomy and 5000 rads of radiation to the chest and
Requests for reprints should be addressed to Richard J. Seime. Department Virginia University Medical Center, Morgantown, WV 26506. U.S.A.
61
of Behavioral
Xledicine and Psychiatry,
West
hZ
P.AUL C
GREENE
regional Ivmph nodes. In 1W a bone scan revealed multiple metastases and she underwent further radiation therapy of 3000 ruds to her lumbar spine. Folloiving radiation, she was started on a treatment protocol consisting of Cytosan. Adriamycin and 5 FU administered in a 23 dav cvcle. A total dose of Adriamycin (37s m:) ~
patient was observed during six The consecutive chemotherap), trcatmr_‘nts. The initial assessment conducted during 2 rcgularlq scheduled treatment identified anticipatorv s> mptoms consistin 2 of complaints of nause;l, verbal complaints of ansicty, verbal complaints of taste sensations, gaggindretching and spitting. These behaviors ivere targeted as drpendent measures to evaluate treatment effects. Following initial observation. the conditionin: model of anticipatory n;iusea and vomiting w;is explained to Sandr;i. A solution composed of zqu2l parts of lemon juice and water was SUggeSted ;IS ;I masking agent to disguise taste sensations associated \vith nausea. This solution \V;IS made available on an (111 lib. basis during the next three consecutive treatments. The solution was orally administzrtxi by a consultant in 0.5 cm-’ doses using ;I 3 cm-’ syringe. Dose frequency V.XSdetermined by the patient. Following this intervention, she W;IS observed at two subsequent treatments during which the lemon
cind RICH.-\RD
J
SEIXLE
solution \vas not administered in order to evaluate the maintenance of treatment effects. After the second follou-up treatment Sandra \VX admitted to the hospital and subsequentI> died of pulmonary complication. During each chemotherapy treatment a time samplin? procedure uas used to record the occurrence/non-occurrence of t’;tch of the targeted behaviors in a sequence of conwcutive 15 s intervals. The frequency of each behavior was reported as the number of sample intervals in lvhich that behavior MS observed.
RESULTS One occurrence of each of thf targeted behaviors M’;~s recorded during Treatment I (pre-intervention). At Treatment 2 (taste masking intervention) the patient requested seven doses of lemon juice. Spitting bvus recorded in three of the sample intervals. Verbal complaint of anxiety was recorded in onr: intt‘rval. At Treatment 3 Sandra requested three doses of lemon juice. Konz of the tarpcteci behaviors were otwrved. Shz rcquested tbvo doses of lemon juice at Treatment 4. Verbal complaint of an unpleaant taste \\‘;Is recorded in one sample interval. Follo~v-up observations were made during the t\vo subsequent chemotherapy trc‘atmznts. The maskins agent was not available during these treatments. At Treatment 5 \,erbal complaint of anxiety was rwordcd in one sampIt interval. Verbal complaint of an unpleasant taste ~2s recorded in one sample interval at Treatment 6.
DISCUSSION A decrease in anticipatory symptoms was observed across the course of tht six chemotherapy treatments. Drug dose and the LISZ of antiemetics. t\vo potential confounds. were constant across Treatments 1 and 2 (100% chemotherapy dose. no antiemetic). Holding these variables constant. threk of thz five targeted behaviors were eliminated with the
STI?.lULtiS
GAG/RETCH
* c, 3
SPIT
NlUSE
‘1
/
2
A
c, Y
3
2
de
.
TASTE 0.
2
ANXIETY
0
i+
8 6 LEMON
SOLUTION
4
( 5 cc doses) 2
THORAZINE
2i
Ir.
(mql s CHEMOTHERAPY
,Cg
WI 0
* 2
3
CHEMOTHERAZY
4
5
6
TREATMENTS
introduction of the masking agent at Treatment 2. Although treatment effects were confounded by dose reduction and by the administration of Thorazine, the patient‘s medical records document severe anticipatory qmptoms regardless of drug dose. A retrospective baseline also indicates that anticipatory symptoms were not relieved by antiemetics. Furthermore. _ gagging/retching verbal and complaints of nausea were not observed at Treatments 2 and 5 even though Thorazine was
fl3
CONTROL
not administered. Targeted behaviors did not vary systematically with drug dose. The observed treatment effects are related to the introduction of the masking agent. It is possible that the masking agent disgrised taste sensations associated with nausea. In the absence of this conditioned stimulus. anticipatory symptoms were not elicited. It is also possible that social demand characteristics could account for the decrease in symptoms. However. all chemotherapy treatments uere administered in an open clinic area where the patient could be readily observed by members of the nursing staff and other patients. Thus, social constraints and attention from staff were present at all treatments but did not inhibit anticipatory symptoms prior to the taste masking intervention. A definite statement about treatment effects cannot be made without more precise esperimental control of relevant variables. Nevertheless, the case is of considerable heuristic value in that it introduces a clinical intervention based on the commonly accepted hypothesis that anticipatory nausea and vomitresponse. Treatment ing is a conditioned effects consistent with this hypothesis suggest that stimulus manipulations used in a classical conditioning paraciigm may have clinical utility in the trcatmcnt of anticipatory nausea and vomiting. Systematic clinical application of stimulus manipulation procedures is needed to support the utility of this approach and to identify the variables that mediate the trcatment effects.
REFEREXCES Borison H. L. and McCarthy cology of chemothcrap) (Suppl. I). s-17.
L. E. (19s.;) Neuropharma~nduccd em&b. Ltricg> 25.
64
PAUL
G.
GREESE
and RICHARD
hlorrow G. R. and Xlorrsll C. (15X32) Behavioral treatment for the anticipatory nausea and vomiting induced by CSIICST chemotherapy. New Engfand /. Med. 307.
147t-llsO. Sersnz D. R.. Levrnthal H.. Lo,re R. R.. Coons J. and Ringler K. (1952) Ansiety and tastes of drugs dunng Injections as predictors of anticipatory nausea in cuncer chemotherapy. Unpublished manuscript.
J. SEIME
Xesse R. Xl., Carl1 T.. Curtis G. C. and Kleinman P. D. (1980) Pretreatment nausea in cancer chemothsrap>: A conditioned response’? f’sychosom. ,Mrd. 12, 3;36. Rsdd LV. H. and Andrrsrn G. V. (1981) Condltionsd clversion in cancer patients. Brhar. Thhrr 1. 3-4
,-\cXnowlrdgrnrrnrs - The authors thank William Reed. Ph.D. for his helpful comments on an earlier vrrslon manuscript. Xppreciatlon is albo eutendsd to Barbara Carr and Catherine W’entz of the Hematology/Oncology nurslns staff for their assistance and cooperation In this project.
of this Clinic
CONTROL
PAUL
OF ANTICIPATORY CHEMOTHERAPY G. GREENE
and RICHARD
NAUSEA
IN CANCER
J. SEIME
Department
of BehavioralMedicine
Summary manipulation old female conditioned anticipatory maintained
A single subject ABA design was used to evaluate the effect of a stimulus on anticipatory nausea. A lemon soIut1on was orally administered to a hl-yearoncology patient in order to mask taste sensations thought to function as a stimulus eliciting anticipatory symptoms durin g chemotherapy. A decrease in symptoms was observed with the introduction of the taste masking agent and was following withdrawal of the agent.
and Psychiatry.
West Virginia
Universir)-
b1edica.l Center
manipulations might be effective in the management of anticipatory nausea and vomiting. Manipulations that disrupt the predictive relationship between the conditioned stimulus and the unconditioned stimulus should allow the conditioned nausea to extinguish. It should also be possible to eliminate anticipatory nausea and vor_niting by removing or significantly altering the stimuli assumed to elicit the conditioned response. Taste sensations experienced during drug injection have been associated with the development of anticipatory nausea (Nerenz et al., 1982) and may in fact act as conditioned stimuli capable of eliciting it. The following case study represents the use of a masking stimulus to obscure taste sensations thought to function as a conditioned stimulus eliciting anticipatory nausea and gagging behavior.
The emetic potential of antineoplastic agents used in the treatment of cancer has been well documented (Borison and McCarthy, 19S3; Laszlo, 1983). Nausea and vomiting induced by these drugs begins approximately one or two hours after injection and can persist for as long as 24 hours (Moertel and Reimeier, 1969). After receiving several chemotherapy treatments, many patients begin to experience these side effects even before the drugs are administered. Anticipatory nausea and vomiting has been described as a conditioned response (Morrow, 1982; Neese, et al., 1980; Redd and Andersen, 1981). Initially, nausea and vomiting (unconditioned response) are automatically elicited by the antineoplastic agent (unconditioned stimulus). Cues in the environment that reliably predict the administration of chemotherapy gradually become conditioned stimuli capable of eliciting a conditioned response (anticipatory nausea and vomiting). On the basis of this conditioning model, relaxation has been used as a learned response that is incompatible with nausea and vomiting and capable of reducing the severity of these symptoms (Morrow and Morrell, 1982). The conditioning model also suggests that stimulus
CASE
HISTORY
Presenting problem The patient, Sandra, a 61-year-old Caucasian female. was initially diagnosed with intraductal breast cancer in 1979. At that time, she underwent a right modified radical mastectomy and 5000 rads of radiation to the chest and
Requests for reprints should be addressed to Richard J. Seime. Department Virginia University Medical Center, Morgantown, WV 26506. U.S.A.
61
of Behavioral
Xledicine and Psychiatry,
West
hZ
P.AUL C
GREENE
regional Ivmph nodes. In 1W a bone scan revealed multiple metastases and she underwent further radiation therapy of 3000 ruds to her lumbar spine. Folloiving radiation, she was started on a treatment protocol consisting of Cytosan. Adriamycin and 5 FU administered in a 23 dav cvcle. A total dose of Adriamycin (37s m:) ~
patient was observed during six The consecutive chemotherap), trcatmr_‘nts. The initial assessment conducted during 2 rcgularlq scheduled treatment identified anticipatorv s> mptoms consistin 2 of complaints of nause;l, verbal complaints of ansicty, verbal complaints of taste sensations, gaggindretching and spitting. These behaviors ivere targeted as drpendent measures to evaluate treatment effects. Following initial observation. the conditionin: model of anticipatory n;iusea and vomiting w;is explained to Sandr;i. A solution composed of zqu2l parts of lemon juice and water was SUggeSted ;IS ;I masking agent to disguise taste sensations associated \vith nausea. This solution \V;IS made available on an (111 lib. basis during the next three consecutive treatments. The solution was orally administzrtxi by a consultant in 0.5 cm-’ doses using ;I 3 cm-’ syringe. Dose frequency V.XSdetermined by the patient. Following this intervention, she W;IS observed at two subsequent treatments during which the lemon
cind RICH.-\RD
J
SEIXLE
solution \vas not administered in order to evaluate the maintenance of treatment effects. After the second follou-up treatment Sandra \VX admitted to the hospital and subsequentI> died of pulmonary complication. During each chemotherapy treatment a time samplin? procedure uas used to record the occurrence/non-occurrence of t’;tch of the targeted behaviors in a sequence of conwcutive 15 s intervals. The frequency of each behavior was reported as the number of sample intervals in lvhich that behavior MS observed.
RESULTS One occurrence of each of thf targeted behaviors M’;~s recorded during Treatment I (pre-intervention). At Treatment 2 (taste masking intervention) the patient requested seven doses of lemon juice. Spitting bvus recorded in three of the sample intervals. Verbal complaint of anxiety was recorded in onr: intt‘rval. At Treatment 3 Sandra requested three doses of lemon juice. Konz of the tarpcteci behaviors were otwrved. Shz rcquested tbvo doses of lemon juice at Treatment 4. Verbal complaint of an unpleaant taste \\‘;Is recorded in one sample interval. Follo~v-up observations were made during the t\vo subsequent chemotherapy trc‘atmznts. The maskins agent was not available during these treatments. At Treatment 5 \,erbal complaint of anxiety was rwordcd in one sampIt interval. Verbal complaint of an unpleasant taste ~2s recorded in one sample interval at Treatment 6.
DISCUSSION A decrease in anticipatory symptoms was observed across the course of tht six chemotherapy treatments. Drug dose and the LISZ of antiemetics. t\vo potential confounds. were constant across Treatments 1 and 2 (100% chemotherapy dose. no antiemetic). Holding these variables constant. threk of thz five targeted behaviors were eliminated with the
STI?.lULtiS
GAG/RETCH
* c, 3
SPIT
NlUSE
‘1
/
2
A
c, Y
3
2
de
.
TASTE 0.
2
ANXIETY
0
i+
8 6 LEMON
SOLUTION
4
( 5 cc doses) 2
THORAZINE
2i
Ir.
(mql s CHEMOTHERAPY
,Cg
WI 0
* 2
3
CHEMOTHERAZY
4
5
6
TREATMENTS
introduction of the masking agent at Treatment 2. Although treatment effects were confounded by dose reduction and by the administration of Thorazine, the patient‘s medical records document severe anticipatory qmptoms regardless of drug dose. A retrospective baseline also indicates that anticipatory symptoms were not relieved by antiemetics. Furthermore. _ gagging/retching verbal and complaints of nausea were not observed at Treatments 2 and 5 even though Thorazine was
fl3
CONTROL
not administered. Targeted behaviors did not vary systematically with drug dose. The observed treatment effects are related to the introduction of the masking agent. It is possible that the masking agent disgrised taste sensations associated with nausea. In the absence of this conditioned stimulus. anticipatory symptoms were not elicited. It is also possible that social demand characteristics could account for the decrease in symptoms. However. all chemotherapy treatments uere administered in an open clinic area where the patient could be readily observed by members of the nursing staff and other patients. Thus, social constraints and attention from staff were present at all treatments but did not inhibit anticipatory symptoms prior to the taste masking intervention. A definite statement about treatment effects cannot be made without more precise esperimental control of relevant variables. Nevertheless, the case is of considerable heuristic value in that it introduces a clinical intervention based on the commonly accepted hypothesis that anticipatory nausea and vomitresponse. Treatment ing is a conditioned effects consistent with this hypothesis suggest that stimulus manipulations used in a classical conditioning paraciigm may have clinical utility in the trcatmcnt of anticipatory nausea and vomiting. Systematic clinical application of stimulus manipulation procedures is needed to support the utility of this approach and to identify the variables that mediate the trcatment effects.
REFEREXCES Borison H. L. and McCarthy cology of chemothcrap) (Suppl. I). s-17.
L. E. (19s.;) Neuropharma~nduccd em&b. Ltricg> 25.
64
PAUL
G.
GREESE
and RICHARD
hlorrow G. R. and Xlorrsll C. (15X32) Behavioral treatment for the anticipatory nausea and vomiting induced by CSIICST chemotherapy. New Engfand /. Med. 307.
147t-llsO. Sersnz D. R.. Levrnthal H.. Lo,re R. R.. Coons J. and Ringler K. (1952) Ansiety and tastes of drugs dunng Injections as predictors of anticipatory nausea in cuncer chemotherapy. Unpublished manuscript.
J. SEIME
Xesse R. Xl., Carl1 T.. Curtis G. C. and Kleinman P. D. (1980) Pretreatment nausea in cancer chemothsrap>: A conditioned response’? f’sychosom. ,Mrd. 12, 3;36. Rsdd LV. H. and Andrrsrn G. V. (1981) Condltionsd clversion in cancer patients. Brhar. Thhrr 1. 3-4
,-\cXnowlrdgrnrrnrs - The authors thank William Reed. Ph.D. for his helpful comments on an earlier vrrslon manuscript. Xppreciatlon is albo eutendsd to Barbara Carr and Catherine W’entz of the Hematology/Oncology nurslns staff for their assistance and cooperation In this project.
of this Clinic