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Psychiatric aspects of cancer
LINDA GAY PETERSON, M.D. MICHAEL K. POPKIN, M.D. RICHARD C.W. HALL, M.D.
Psychiatric aspects of cancer The authors review the psychiatric symptoms that may precede, accompany, and follow the onset of cancer. Difficulty in expressing anxiety, depression, or anger and low scores on these parameters in psychological testing along with depression and feelings of hopelessness are linked with the emergence of malignant tumors. Cancers of the brain, pancreas, and other endocrine organs, and hormone-secreting tumors frequently develop following the appearance of psychiatric symptoms. The psychological adjustment of cancer patients and the more common psychiatric sequelae of malignancy and its treatment are examined. The authors emphasize the need for careful assessment and attention to the biologic, psychological, and social factors critical to the patient's response and adjustment to the disease. stress were involved in the etiology of cancer.' Although, more recently, there have been accounts of spontaneous remissions of cancer attributed to personal faith as well as reports of rapidly accelerating malignancies in patients who have become depressed or suffered losses, an objective, systematic as-
sessment of the interaction of mental health and cancer is needed. The scientific community has long struggled with the intriguing possibility of cause and effect relationships between psychopathologic conditions and cancer. In fact, in 1966 the Annals of the New York Academy of Science devoted an entire issue to the topic.2 Unfortunately, 15 years later little clarification has emerged. Remaining unresolved is the role of psychological stress or psychiatric illness in the etiology of cancer. In this report, the available data on the relationship of psychopathology and cancer will be reviewed in terms of stages of malignancyprecancerous, early development, and the subsequent clinical course. Treatment and outcome will be considered with respect to the relationship between cancer and psychiatric illness.
Dr. Peterson is assistant prOfessor ofpsychiatry, University of Texas Medical School at Houston; Dr. Popkin is associate professor ofpsychiatry and medicine, University of Minnesota Medical School; and Dr. Hall is prOfessor ofpsychiatry and medicine, Medical College of Wisconsin, Milwaukee. Reprint requests to Dr. Peterson, PO Box 20708. 6431 Fannin, Houston, TX 77025.
Psychopathologic precursors to cancer The relationship between psychological stress and the development of cancer has interested physicians
ABSTRACT:
For centuries malignant tumors and mental health have been linked in the minds of both laymen and physicians. Galen observed that melancholic women seemed to develop cancer more frequently than sanguine women. In the 18th and 19th centuries, Guy, Paget, and Snow argued that depression and
(continued) 774
PSYCHOSOMATICS
Cancer: Psychiatric aspects
for many years. LeShan3 reviewed literature published between 1902 and 1957, which associated life stresses and psychiatric illness with the development of cancer. There were no controlled studies; the reports consisted of clinical vignettes. Depression, hopelessness, and grief emerged as frequently cited precursors of cancer. In 1976, Hurst 'and associates" reviewed studies from the late 1950s to the early 1970s linking depression and anxiety with the subsequent development of malignant tumors. In one prospective study, 1076 Johns Hopkins University medical students were observed for II to 27 years after initial psychological testing. The investigators found that nine subjects who later developed cancer had initially lower scores on depression, anxiety, and anger than those of students who subsequently developed mental illnesses and those of control subjects.5 In a ten-year follow-up study of 2550 Swedish citizens, Hagnell6 noted personality differences between persons who developed cancer and those who did not. He described the group developing cancer as "substable," showing more energy loss and withdrawal when depressed than their healthy counterparts. Since standard diagnostic nomenclature was not used in this study, it is difficult to compare with others. Kissen,7 Kissen and associates,8 and Abse and associates9 noted lower neuroticism scores on the Eysenck Personality Inventory by cancer patients, particularly those with lung cancer, than by other medical patients or normal control subjects. Patients in these studies were tested during hospitalizations for diagnostic evaluation. Accordingly, their Eysenck test scores
probably reflected preexisting personality patterns rather than sequelae of their illness. Studies by Huggan 'O in 1974 and by Greer and Morris " in 1975 on women with breast cancer demonstrate similar findings including extreme suppression of anger and, in elderly patients, suppression of other feelings as well. These observations differed from earlier research describing patterns of extraversion,'~ stress preceding the illness,1) and depression '4 in women with breast cancer. While these earlier studies
In human depressiollt increased cortisol levels and depressed function of T cells have been noted. usually included patients already diagnosed, Greer and Morris " evaluated 160 women just admitted for breast biopsies. Studies assessing affective state and life events proximate to the development of malignancy were done by LeShan and Worthington,15 Greene,16 and Bahnson and Bahnson. 17 Their findings all suggest that the loss of an intensely dependent relationship frequently occurs shortly before the clinical onset of cancer. Schmale and Iker '8 evaluated patients undergoing cone biopsies of the cervix. Based on the patients' reported feelings of hopelessness, the investigators made correct predictions of the biopsy results in more than two thirds of the cases. A similar study by Muslin and associates '9 did not identify recent loss as predictive of the outcome of breast biopsy in a series of 165 patients. The difference between loss (a life event) and hopelessness (a cognitive ap-
praisal of an event) may account for the disparity between the two studies. The discrepancy also might be related to the difference in the types of malignancy that were studied. Animal research by several groups shows that early traumatic experiences with rearing, the development of experimentally induced neurosis, and social stress may each impair immune response and increase vulnerability to the development and rapid spread of experimentally produced cancer.~o In human depression, increased cortisol levels and depressed function of T cells have been noted.21 Given the increased incidence of cancer in patients whose immune response has been suppressed for other reasons, it is possible that the immunosuppression associated with depression might be a mediating factor in cancer. Kerr and associates22 described a characteristic form of depressive illness that appeared to be a frequent precursor of cancer. Five of 28 males hospitalized with the diagnosis of depression later died of cancer. The number of deaths was greater than would be expected in an age-matched sample of the general population. All five men had depressive illness developing in middle age without apparent cause and without a history of psychiatric illness. The clinical picture was varied and included features of both reactive and endogenous depression. The immediate response to ECT and antidepressants was good, but transient. However, more extensive studies reviewing the incidence of malignancy in depressed patients have not confirmed the findings of Kerr and associates. Evans and associates23 reviewed the records of 823 patients hospi(conlin lied)
SEPTEMBER 1981 • VOL 22 • NO 9
779
Cancer: Psychiatric aspects
talized with a diagnosis of depression. In a four-year follow-up study, they found no increase in morbidity and mortality from malignancy. In Finland, Niemi and laaskelainen24 at ten- and 20-year intervals observed two groups of patients (N = 191) with the diagnosis, according to Feighner's criteria, of depressive illness. There was no significant increase in morbidity or mortality secondary to malignant disease. These two studies do not support the thesis that patients with depressive illness are at increased risk of developing cancer. Reports of hopelessness and depression immediately preceding a diagnosis of cancer may reflect a more general phenomenon of "giving up" which predates many medical illnesses, as discussed by EngelP Such a phenomenon might be explained by an underlying process causing both mood alteration and the clinical appearance of disease. This theory is supported by the increased incidence of psychiatric illness, especially affective, in patients with endocrine disturbances. Perhaps an internal feedback loop involving the immune, endocrine, and limbic systems contributes to the concurrent appearance of psychological and physical symptoms (see the Figure). The question of a relationship between depression and cancer is complicated by recent suggestions that psychotropic agents used to treat depression may contribute to an increased incidence of breast cancer.26 -28 Two subsequent studies, however, challenge this finding. 29 .3o The development of cancer has been thought to be inversely related to the development of schizophrenia. Rassidakis and associatesl ' noted a lower than expected SEPTEMBER 1981 • VOL 22 • NO 9
death rate from cancer among schizophrenic patients. They cited similar data in other European studies. Fox and Howell 32 suggested that this lower incidence may be ascribed to lifestyle differences between the general population and chronically hospitalized patients. Reports by Dynes33 and Ananth and Burnstein34 did not show a decreased incidence of malignancy among schizophrenic patients in the United States. At present, it seems premature to conclude that either schizophrenia or its treatment lowers the incidence of neoplastic disease. In conclusion, the data supporting specific connections betweeen psychiatric illness or psychological stress and the development of neoplastic disease are limited and largely retrospective. However, personality factors may be related to an increased incidence of malignancy in later life. Further, there appears to be a significant relationship between object loss, associated depression, and the clinical onset of at least some types of malignancy. Psychiatric presentations of cancer Reports of psychiatric symptoms in cancer patients have both theoretical and practical importance. Such
reports should heighten suspIcIon of malignancy in patients whose symptoms might otherwise be dismissed as functional. Understanding the mechanisms by which tumors of the central nervous system and endocrine glands, and other tumors produce psychiatric symptoms may, in turn, increase our understanding of the mechanisms underlying psychiatric illnesses currently thought to be functional. A careful review of the pertinent literature reveals numerous reports of patients with carcinomas of the pancreas who initially presented with psychiatric symptoms. In 1951 Soniat35 noted the association of psychiatric symptoms and intracranial neoplasms. More recently investigators have described psychiatric symptoms in patients with tumors of the endocrine system or with hormone-secreting tumors.36•40 Case reports and review articles in the last decade show increased attention to cancer patients who have behavioral abnormalities.40·41 But these studies often lack precise descriptions of the psychiatric symptoms, particularly those associated with organic mental disorders. Comments are usually limited to characterizations of mood state or grossly psychotic behavior. (continued)
Psychological stress
Physical stress
I
I
Affective response via limbic system
~
Immune response
Endocrine response (cortisol production)
FIG U RE-Hypothesizedfeedback loop involves the immune. endocrine, and limbic systems. 783
Cancer: Psychiatric aspects
The Table lists representative case reports of the last ten years.36.39 .42.49 In 37 case reports during that period, tumors of the central nervous system were preceded by psychiatric symptoms. Four of these were gliomas, five were cholesteatomas, and 20 were meningiomas. The interval from the observation of psychiatric symptoms to the subsequent diagnosis of the malignancy ranged from one to eight years. The psychiatric symptoms most commonly reported varied with the location of the tumor. Tumors of the spinal cord and brainstem most often were preceded by "conversion" symptoms. The earliest behavioral changes in patients with frontal lobe tumors included depression, apathy, and schizophreniform features. This range of psychiatric symptoms is comparable to that reported with frontal lobe disease generally.50 One patient found to have a tumor of the lateral ventricle initially had a psychosis including hallucinations, delusions, and pressured speech. Of the 37 case reports, a thorough neuropsychological evaluation of only eight patients was conducted. In each of these cases there was evidence of cognitive impairment accompanying mood and thought disturbances. Case reports in the last decade describing psychiatric presentations of endocrine and hormonesecreting tumors include 22 cases of carcinoid, one case of adenomatosis, and one of pheochromocytoma (see Table). Although reports associating psychiatric symptoms with thyroid dysfunction date back to 1888,51 no new reports of thyroid tumors with accompanying psychiatric symptoms were found in the literature of the last ten years. In the Table, the majority of patients 784
with tumors of the endocrine organs or with hormone-producing tumors had depression or anxiety. (The patient with adenomatosis exhibited aggression.) With the exception of a case of an ACTH-secreting oat cell carcinoma reported by Anderson and McHugh,36 there is no documentation of mental status findings or neuropsychological testing to distinguish organic mental disorders with affective symptoms from affective states with no known organic cause. In 1923 Scholz and Pfeffe~2 first described "nervousness" in patients preceding the diagnosis of carcinoma of the pancreas. In the last several years there have been two excellent articles addressing psychiatric issues in carcinoma of the pancreas. Fras and associates53
Weight loss and weakness were associated with all gastrointestinal tumors, but depression and irritability appeared to be linked only to carcinoma of the pancreas. in the United States and Jacobsson and Ottosson47 in Sweden both reviewed earlier literature and presented their own data. Jacobsson and Ottosson retrospectively determined the incidence of psychiatric symptoms in a series of patients with pancreatic carcinoma. Fras and associates53 evaluated newly diagnosed cases ofcarcinoma of the pancreas and other gastrointestinal tumors to determine the incidence and type of psychiatric symptoms. Of Jacobsson's and Ottosson's cases, 14% (8 of 57) had psychiatric symptoms, while 48% (22 of46) had psychiatric symptoms in Fras and associates' study. In both these and
other studies cited in the Table, psychiatric symptoms appeared from one to 43 months before the diagnosis of carcinoma. The most common constellation of symptoms included depression with weakness, irritability, and weight loss. Weight loss and weakness were associated with all gastrointestinal tumors, but depression and irritability appeared to be linked only to carcinoma of the pancreas. In Fras and associates' study, careful neuropsychological testing showed no evidence of organic mental disorder in any of the 46 patients. Psychiatric symptoms accompanying advanced cancer The incidence and nature of psychiatric symptoms among cancer patients have been discussed by Levine and associates.4o Depression appears to be the most frequently reported of these symptoms, cited in approximately 25% of patients. However, Plumb and Holland41 noted that this incidence is comparable to that among medical inpatients of all diagnoses. Organic mental disorders were present in 50% of the cases seen by Levine and associates.4o No other carefully documented series is available. Substantial psychological stress may be attendant on the diagnosis of cancer and on the subsequent physical ravages of the disease. Factors that may strongly influence psychological functioning include: (I) the reaction to the diagnosis by patient and family; (2) the patient's previous patterns of stress response (i.e., coping); (3) the direct effects of the cancer on the nervous system; (4) the indirect effects of cancer, especially alterations in metabolism; and (5) the effects of cancer treatment. The impact of the diagnosis inPSYCHOSOMATICS
Table-Cancer Preceded by Psychiatric Symptoms
Type of tumor
Loc8tIon of
Invedg8tor(a)
(N)
tumor
Burch at al42
Glioma (1)
Brain stem
Buchanan and Abrams43
Meningioma (1 )
Epstein et al 44
P.........nll psychlllllle aymptoma
Ment8I .......
Ut8nc1from
Of~
recognition 01 .....18IrIc 8f"IPI01H to
Iogleel tMIIng reported/OrpnIc mental symptoma mentioned
""1801
Conversion symptoms Hysterical neurosis
No/No
3}i yr
Lateral ventricle
Psychosis Pressured speech
Yes/Yes
<3wk
Multiple (27)
Spinal cord
Hysterical neurosis. conversion type
No/No
1-8 yr
Avery45
Meningioma (7)
Frontal lobe
Depression Apathy
Yes/Yes
4 wk-6 yr
Cole46
Oligodendroglioma (1)
Fron~al
Schizophrenia
No/Yes
6yr
Anderson and McHugh36
Oat cell carcinoma (1)
.Lung
Depression Suicide attempt
Yes/No
several days
Gilmer'l7
Pheochromocytoma (1)
Organs of Zuckerkandl
Depression
Yes/No
several days
Major et al38
Carcinoid (22)
Depression Anxiety
No/No
Not known
Carney et al39
Adenomatosis (1 )
Aggression
NoNes
None
Jacobsson and Ottosson 47
Pancreatic carcinoma (8).
Pancreas
Irritability Weakness Depression
No/No
6 wk-1% yr
Wallen et al 48
Pancreatic carcinoma (1)
Pancreas
Depression
No/No
2wk
Arbitman4g
Pancreatic carcinoma (1)
Pancreas
Depression Anxiety
No/No
10 mo
SEPTEMBER 1981 • VOL 22'
09
lobe
C8I1cer
785
................... ,.......
..,..t.,.~
...,
8efcIl-. prMCrIblng, ,..... conault comp1et8 product Infonn8tlon• • sumnwry of wtllCh follows: Indlc:etlons: Management of anxiety disorders. or short·term relief of symptoms ot anxiety. Anxiety or tension associated with the stress of ellllryday life usually does not require treatment with an anxiolytic Symp· tomatic reliet of acute agitation. tremor. impending or acute delirium tremens and hallucinosis due to acute alcohol withdrawal: ad;unctively in relief 01 skeletal muscle spasm due to reflex spasm to local pathology; spasticity caused by upper motor neuron disorders; athetosis; s@·man syndrome Oral form may be used adJunctlliely in convulsive disorders, but not as sole therapy Injectable form may also be used adJunctiliely In status epilepticus. sellere recurrent seizures. tetanus; anxiety. tension or acute stress reactions prior to endoscopic/surgical procedures; cardioversion The effectiveness 01 Valium (diazepam/Roche) In long.term use. that is. more than 4 months. has not been assessed by systematic clinical studies The phySician should periodically reassess the usefulness 01 the drug lor the individual patient eomqlncllC8tlona: Tablels in children under 6 months 01 age. known hypersensitivity. acute narrow angle glaucoma, may be used in patients with open angle glaucoma who are receiving appropnate therapy Wunlnga: As with most CNS·aCling drugs, caution against hazardous occupalions reQuinng complete mental alertness (e.g, operating machinery. driving) Withdrawal symptoms Similar to those With barbiturates and alcohol have been observed with abrupt discontinuation. usually limited to extended use and excessive doses InlreQuently, milder withdrawal symptoms have been reported 10llOWlng abrupt discontinuation 01 benzodiazeplnes after continuous use, generally at higher therapeutic lellels, tor at least several months After extended therapy, gradually taper dosage Keep addictlonprone Individuals (drug addicts or alcoholics) under caretul surveillance because of predisposition to habituation/dependence
UNge In PregrIency: U.. 01 minor tqnqullizers dUring flm trimester ahould almost alwsya be .wlded beceu.. oIln_ _ rlak 01 congennel malformetlona, .a auggntad In ..".,.1 stud.... eonaldal' posslblilty of pregnancy when Instituting therapy; advl. . patlenta to dlKuaa therapy If they Intand to or do becoma pregnant. ORAL Advise patients against simultaneous ingestion 01 alcohOl and other CNS depressants Not of value ,n treatment of psychotic patients. should not be employed In lieu 01 appropnate treatment When USing oral IorIO adlunctively in convulSive disorders, possibility 01 increase in IreQuency and/or seventy 01 grand mal seizures may reqUire Increase In dosage ot standard anticonvulsant medica· tion, abrupt Withdrawal in SUCh cases may be associated With temporary Increase in frequency and/or severity 01 seizures INJECTABLE To reduce fhe pOSSibility of venous thrombOSIS. phlebilis. local Iff/lalion. swellmg, and, rare/y, vascular Impalfmenr when used I V m/eCI slowly. takmg at leasl one minule for each 5 mg (I mlj given. do not use small vems. Ie. dorsum of hand or Wf/st, use extreme care to aVOid mtra-artef/al admlOistratlon or exlravasat,on Do nOI mix or dilule Valium with other solu· t,ons or drugs 10 syringe or mfuSlon lIask II it IS not feasible 10 adminisler Valium dlfectly / V.. It may be mjected slowly through the mfuSlon tubmg as close as possible 10 /he vein mser/IOn Administer With exlreme care to elderly. very ill. those With limited pulmonary reserlle because of poSSibility of apnea and/or cardiac arrest. concomitant use 01 barbiturates, alcohol or other CNS depressants increases depreSSion With Increased risk of apnea. have reSUSCitative lacilities available When used with narcotic analgeSIC eliminate or reduce narcotic dosage at least '!:l. administer in small increments Should not be administered to paMnts In shock, coma, acute alcoholic intOXication With depression of vital signs Has precipitated tonic status epilepticus In patients treated lor petit mal status or petit mal van ant status Not recommended for OB use Efficacy/salety not established In neonates (age 30 days or less); prolonged eNS depreSSion observed In children. give slowly (up to 0 25 109/kg over 3 minutes) to aVOid apnea or prOlonged somnolence, can be repeated after 15 to 30 mmutes If no reliel after third administration. appropnate adJunctive therapy IS recommended PNcautlona: If combined With other psychotroplCS or antlconvulsants. carefully conSider ,ndiVidual pharmacologic effects-particularly With known compounds which may potentiate action of Valium (diazepam/Roche), Ie. phenoth;azines. narcotics. barbiturates. MAO Inhibitors and antidepressants Protective measures indicated ,n highly anxIOUS patients With accompanYing depreSSion who may have SUICidal tendenCies Observe usual precautions In impaired hepatiC lunctlon; avoid accumulahon In patients with compromised kidney lunchon Limit oral dosage to smallest effective amount in elderly and debilitated to preClude ataxia or oversedat,on (Initially 2 to 2'1:1 109 once or twice dally. Increasing gradually as needed or toleraled) The clearance of Valium and certain other benzodiazeplnes can be delayed ,n association With Tagamet (Clmetidine) administration The clinical Significance of thiS is unclear INJECTABLE Although promptly controlled. seizures may return. re·administer if necessary. not recommended for long-term maintenance therapy Laryn· gospasm/increased cough reflex are POSSible dunng peroral endoscopic procedures, use topical anesthetiC. have necessary countermeasures available Hypotension or muscular weakness possible, particularly when used with narcotics, barbiturates or alcohOl Use lower doses (2 to 5 109) lor elderly/debilitated ~ Reactions: Side effects most commonly reported were drowsi· ness. fatigue. ataxia Infrequently encountered were confusion. constipation. depression. diplopia. dysarthria. headache. hypotension. incontinence. Jaundice. changes in libido. nausea. changes in salivation. skin rash. slurred speech. tremor. urinary retention, llertigo. blurred vision: Paradoxical reac· tions such as acute hyperexcited states. anxiety. hallUCinations. Increased muscle spasticity. insomnia. rage. sleep disturbances and stimulation have been reported, should Ihese occur. discontinue drug Because of isolated reports 01 neutropenia and Jaundice. periodic blOod counts. Iiller function tests advisable during long·term therapy. Minor changes in EEG patterns, usually low·voltage last activity. have been observed in patients during and after Valium (diazepam/Roche) therapy and are of no known significance INJECTABLE: Venous thrombOSIS/phlebitis at injection site. hypoactivity. syncope, bradycardia, cardiovascular collapse, nystagmus. urticana. hiccups. neutropenta In peroral endoscopic procedures. coughing. depressed respiration, dyspnea. hyperventilation. laryngospasm/pain in throat or chest have been reported. Management 01 o-doHga: Manifestations Include somnolence. confusion. coma. diminished reflexes Monttor resptrahon. pulse. blood pressure. employ general supportille measures. IV fluids. adequate airway. Use levarterenol or metaraminol lor hypotenSion DialySIS is of limited value.
®
ROCHE LABORATORIES
IIOCII •
DIVISIon of Holtmann-La Roche Inc Nuney. New Jersey 07110
Cancer: Psychiatric aspects
volves factual knowledge and fictional tradition. Both the astrological connection of cancer with the crab and the portrayal of cancer in stories such as "The Death of Ivan I1yitch" reinforce the dread of the disease. Scores of articles have discussed whether the physician should reveal the diagnosis to the patient and his family. In books as well as movies-the latter often based on successful books (e.g., Love Story, Death Be Not Proud, and Brian's Song)-patients struggle bravely against cancer. Weisman and Worden54 examined the adjustment of patients to cancer during the first 100 days of their illness. They found that psychosocial distress was more important in predicting the patient's ability to cope with cancer and its ramifications than the specific diagnosis or prognosis. In a companion project, Weisman55 found that patients with marital problems, a tendency to repress feelings, and a history of depression had the greatest difficulty coping with their illness. In three separate investigations of patients' responses to the diagnosis of cancer and its treatment, the presence and extent of denial of illness were associated with better psychological adjustment, decreased morbidity, and increased survival.5b.58 Weisman55 has also noted the importance of communication between spouses, and Mclntosh5~ has reviewed literature concerning communication processes and how they affect the patient's adjustment to cancer. Thus, the psychological state of the patient and the nature of the available social support systems affect both adjustment to the illness and the risk of morbidity and mortality. Conversely, cancer and its treatment may impinge on the pa788
PSYCHOSOMATICS
tient's psychological well-being. Anorexia and cachexia, associated with cancer, are likely to cause negative changes in body image and to compromise the capacity for physical pleasure.bo This is compounded by additional direct and indirect effects of cancer on the nervous system.61 Further, chemotherapy also produces complications affecting the central nervous system.62 In addition, the strain on interpersonal relations may have psychological repercussions. In the later stages of cancer, psychological problems are similar to
Psychosocial distress was more important in predicting the patient's ability to cope with cancer and its ramifications than the . specific diagnosis or prognosis. those of other patients approaching death. Responses, which are likely to reflect earlier patterns of coping with stress, may include anger, withdrawal, extreme dependency, ·denial, or'a combination. By knowing the patient's earlier coping styles (e.g., stress response) and un·derstanding his or her theological or . philosophical attitude toward 'death, the physician can intervene ,effectively with the patient in this phase of the illness and the family. Ironically, it is the patient who has a particularly long remission or , survives despite expectations to the contrary who often suffers the most · substantial psychosocial ill effects.bJ :This obserVation is consistent with accounts' of survivors of other se.vere emotional and' physical · stresses, such. as detention , . in a con,
c~ntration camp.64 The following case describes such a survivor.
Case report A 46-year-Old married woman was referred for psychiatric evaluation because of marital problems. Adenocarcinoma of the lung had been dicignosed two years earlier. The patient had not been expected to survive more than six months because of the advanced stage of the cancer at the time of its diagnosis. Four months later she had a spontaneous remission with considerable regression of the tumor. She and her husband stated that their marriage had been good until the preceding year. The patient complained that her husband was no longer interested in sharing activities with her and that he badgered her about painting the house and doing housework. He felt his wife was too demanding and that she had lost interest in him and their children. They reported that following the diagnosis of cancer, they had traveled extensively in the United States and Europe, trying to do as much as possible while the patient was still able to function. With the remission of the tumor, she had continued to spend more time than usual visiting friends around the country. Her husband preferred to settle back into their old routines at home, but he felt guilty about restricting his wife's activities since she did not have 16ng to live. Therap'y ended when the couple began to talk openly about the difficulty of treating the patient as any other family member rather than as a person with the entitlement reserved for the dying. ,Summary
Psychological traits that may make for a predisposition to the developImentofmalignancy includ~ limited expression of depression, anger, and anxiety; and a tendency to respond to stress with decreased energy and emotional withdrawal. Feelings of hopelessness or the loss .' of a significant relationship fre-
quently have been observed near the time of the diagnosis of cancer. Those cancers most likely to be preceded by psychiatric symptoms are brain tumors-particularly in the frontal, temporal, or parietal lobes-endocrine or hormone-secreting tumors, and tumors of the pancreas. The most prevalent psychiatric conditions accompanying malignancies are affective disorders or organic mental disorders. Once cancer has been diagnosed, the patient's adjustment will depend on previous patterns of coping with stress, the quality a':ld availability of, social support systems, the nature of the malignancy, and treatment. Appropriate assessment of the effects of psychological, social, and biologic factors on the person's adjustment is an important way of minimizing the morbidity and mortality of cancer. Support groups for patients and their families and early psychiatric consultation may reduce the risk of severe and intractable reactions to having cancer. Finally, even among those patients who are successfully treated, anxiety, loss of morale, and loss of a sense of well-being may hamper the return to a normal and satisfying life. 0 The authors wish to thank Ms. Sue' Wickham, Ms. Mindy Leifer, and Ms.' Terri Paddock for their invaluable help in the preparation ofthis manuscript. REFERENCES 1. Goldfarb C, Oriesen J, Cole 0: Psychophysi." ological aspects of malignancy. Am J Psychi· atry 123:1545-1552,1967.
2. Bahnson CB, Kissen OM: Psychophysiologi. , cal aspects of cancer. Ann NY Acad Sci
125:773-1055,1966. '.
.
3. LeShan L: Psychological states as factors in . the development of malignant disease: A crit-', ical review. J Nail Cancer Inst 22:1-18,1959.' 4. Hurst MW, Jenkins CD, Rose RM: The relation of psychological stress to onset of medical illness. Annu Rev Med 27:301-312, 1976. , .
e
,
" (continued) ,
SEPT,EMBER 1981· VOL 22' NO 9
789 .
,
TRANXENE~
(elorazepa'e dipotassium)@;
INDICATIONS - For manaoement of anxiety disorders or short-term relief of symptoms of anxiety: for symptomatic relief of acute alcohol withdrawal; for adjunctive therapy in partial seizures. Anxiety or tension associated with stress of everyday life usually does not require treatment with an anxiolytic. Effectiveness in long-term management ot anxiety (over 4 months) not assessed by systematic clinical studies. The physician should periodically reassess usefulness tor each patient. CONTRAlNOICATIONS - Known hypersensitivity to the drug. Acute narrow angle glaucoma. WARNINGS - Not for use in depressive neuroses or psychotic reactions. Caution patients against hazardous occupations requiring mental alertness, such as operating dangerous machinery including motor vehicles. Advise against simultaneous use of other CNS depressants, and caution patients lhat effects of alcohol may be increased. Not recommended for patients under 9. Nervousness, insomnia, irritability, diarrhea, muscle aches, and memory impairment have followed abrupt withdrawal from longterm high dosage. Withdrawal symptoms were reported after abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Use caution in patients having pyschological potential for drug dependence (dependence has been observed in dogs and rabbits).
Pregnancy and lactation: Minor trlnqulllzers should almOlt alnys be avoided IIrst trlmelter. Consider poalbility 01 pregnancy before Initiating tIlerapy. PatIent should consult pllyalcian about dlscontinua· tlon II aile becomes pregnant or plans pregnancy. Do not give to nursing mothers. PRECAUTIONS - Observe usual precautions in depression accompanying anxiety. or in patients with suicidal tendency. or those with impaired renal or hepatic function. 00 periodic blood counts and liver function tests during prolonged therapy. Use small doses and gradual increments in the elderly or debilitated. ADVERSE REACTIONS- Drowsiness. diuiness, various gj. complaints, nervousness. blurred vision, dry mouth, headache. mental contusion. insomnia, transient skin rashes. fatigue, ataxia. genitourinary complaints. irritability. diplopia. depression, slurred speech. abnormal liver and kidney function, decreased hematocrit, decreased systolic blood pressure. INTERACTIONS - Potentiation may occur with ethyl alcohol, hypnotics, barbiturates, narcotics, phenothiazines, MAO inhibitors. other antidepressants. In bioavailability stUdies with normal subjects, concurrent administration of antacids at therapeutic levels did not significantly influence bioavailability of TRANXENE. OVERDOSAGE - Take general measures as for any CNS depressant. SUPPLIED - TRANXENE 3.75.7.5. and t5 mg capsules and scored tablets. TRANXENE-SO Half Strength tl.25 and TRANXENE·SO 22.5 mg single dose tablets. REFERENCES:-l. Snyder SH: Anxiety: The Therapeutic Dilemma. No.2. Management Alternatives. Monograph 970544. 1981. P6-7.2. Sedation reported in normal volunteers 30 minutes after dosing. TRANXENE Drug Monograph 970185.1981. P9.3. Hollister lE: Anxiety: The Therapeutic Dilemma. No.2. Management Alternatives. Monograph 970544, 1981. P 11. 4. Mielke DH, Goethe JW: Anxiety: The Therapeutic Dilemma, No.2, Management Alternatives, Monograph 97-0544, 198t, P31.5. Elimination kinetics of an agent can be closely defined but cannot at present be related to therapeutic or adverse effects. 6. Hollister lE: op cit. p 13. 7. TRANXENE Drug Monograph 97-0185.1981. p 15.
EJ
Abbott Laboratorlesl Abbott Pharmaceuticals, Inc. North Chicago. IL 60064
Cancer: Psychiatric aspects
5. Thomas CB, Greenstreet RL: Psychological characteristics in youth as predictors of five disease states: Suicide. mental illness. hypertension, coronary heart disease. and tumor. Johns Hopkins Med J 132:16-43, 1973. 6 Hagnell 0: The premorbid personahty ot persons who develop cancer in a total populatIon investigated in 1947 and 1957. Ann NY Acad Sci 125:846-855. 1966. 7. Kissen OM: The significance of personality in lung cancer in men. Ann NY Acad Sci 125:820-826. 1966. 8. Kissen OM, Brown Rl. Kissen M: A further report on personality and psychosocIal factors in lung cancer. Ann NY Acad Sci 164:535-545, 1969 9. Abse OW, Wilkins MM, Van de Castle RL, et al: Personality and behavioral characteristics ot lung cancer patients. J Psychosom Res 18:101-113,1974. 10. Huggan RE: Neuroticism and anxiety among woman with cancer. J Psychos om Res 12:215-221,1974. 11. Greer S, Morris T: Psychological attributes of women who develop breast cancer: A controlled study. J Psychosom Res 19:147-153, 1975 12. Coppen A, Metcalfe M: Cancer and extraversion. Sr Med J 2:18-19,1963. 13. LeShan LL: Psychological states as factors in the development of malignant disease: A critical review. J Nail Cancer Insf 22: 1-18, 1959. 14. Hagnell 0: The premorbid personality of persons who developed cancer in a total population Investigated In 1947 and 1957 Ann NY Acad Sci 125:846-855. 1966. 15. LeShan L, Worthington RE: Loss of cathexes as a common psychOdynamic characteristic of cancer patients Psychol Rep 2:183-193, 1956 16. Greene WA: The psychosocial seltlng of the development of leukemia and lymphoma. Ann NY Acad Sci 125:794-801, 1966. 17. Bahnson CB, Bahnson MD: Role of the ego defenses: Denial and repression in the etiology ot malignant neoplasm. Ann NY Acad Sci 125:827-845. 1966. 18. Schmale A, Iker H: The psychological setting of uterine cerVical cancer. Ann NY Acad SCI 125807-813,1966 19 Muslin HL, Gyartas KJ, PleperWJ: Separation experience and cancer of the breast. Ann NY Acad Sci 125:802-806, 1966 20. CriSP AH: Some psychosomatic aspects of neoplasia. Sr J Med Psychol 43:313-332, 1970 21. Bartrop R, Luckhurst E, Lazarus L. et al: Depressed lymphocyte function alter bereavement. Lancet 1:834-836, 1977 22. Kerr TAW, Schapiro K. Roth M: The relalionship between premalUre death and affective disorders. Sr J Psychiatry 115: 1277-1282, 1969 23 Evans NJR. Baldwin JA, Gath 0: The incidence of cancer among ,n-patlents With aftectlve disorders. Sr J Psychiatry 124:518525, 1974. 24. Niemi T. Jaaskelainen J: Cancer morbidity In depressive persons. J Psychosom Res
792
22:117-120,1978. 25. Engel GL: A life seltlng conducive to illness: The giving-up-given-up complex. Ann Intern Med 69:293-299, 1968. 26. Boston Collaborative Drug Surveillance Program: Reserpine and breast cancer. Lancef 2:669-671, 1974 27. Armstrong B, Stevens N, Doll R: Retrospective study of the association between use of rauwolfia derivatives and breast cancer in English women. Lancet 2:627-675, 1974. 28. Heinonen OP, Shapiro S, Tuom,nen L: Reserpine use In relation to breast cancer. Lancet 2:675-677,1974. 29. Overall JE: Prior psychiatric treatment and the development of breast cancer. Arch Gen Psychiatry 35:898-899, 1978. 30. Laska EM, Siegel C, Meisner M, et al: Matched-pairs study of reserpine use and breast cancer. Lancet 2:296-300. 1975. 31. Rassidakis NO, KelepoUis M, Goulis K. et al: On the incidence ot malignancy among schizophrenic patients. Agressologie 14:259-273, 1973. 32. Rox BH, Howell MA: Cancer risk among psychiatric patients: A hypothesis. Int J Epidemio/3:207-208,1974.
33. Dynes JB: Cause of death in schizophrenia. Vir Med Monthly 96:338-340, 1969. 34. Ananth J, Burnstein M: Cancer: Less common in psychiatric patients? Psychosomatics 18:44-46,1977. 35. Soniat TlL: Psychiatric symptoms associated with Intracranial neoplasms. Am J Psychiatry 108:19-22,1951. 36. Anderson AE, McHugh RP: Oat cell carcinoma with hypercortisolemia presenting to a psychiatriC hospital as a suicide attempt. J NervMentDis 152:427-431, 1971. 37. Gilmer RE: Phaeochromocytoma-An interesting psychiatric presentation. S AIr Med J 46:174-176.1972. 38. Malor LF, Brown GL, Wilson WP: Carcinoid and psychiatric symptoms. South Med J 66787-790,1973. 39 Carney MWP, Jackson F, We,nbren I. ef al: Multiple adenomatosIs presenting with psychiatric manifestations. Postgrad Med J 47:242-243, 1971. 40. LeVine PM, Silberfarb PM, Lipowski ZJ: Mental disorders in cancer patients: A study of 100 psychiatric referrals. Cancer 42:12851291,1978 41. Plumb MM, Holland J: Comparative studies of psychological function in patients with advanced cancer. I. self-reported depressed symptoms. Psychosom Med 39:264-276. 1977 42 Burch EA. Hutch,son CF. Still CN: Hysterical symptoms masking brain stem glioma. J Clin Psycho/39:75-78.
43. Buchanan DC, Abram HS: Psychotic behavIor resulting from a lateral ventricle meningioma: A case report. Dis Nerv Syst 36:400401,1975 44. Epstein BS, Epstein JA. Poslel OM: Tumors of the spinal cord simulating psychiatric disorders. Dis Nerv Syst 32:741-743,1971. 45. Avery Tl: seven cases ot frootal tumour With
PSYCHOSOMATICS
psychiatric presenlation. Br J Psychiatry 119: 19-23. 1971. 46. Cole G: The masking of organic brain disease by a schizophrenia-like illness. S Afr Med J 47:731-733.1973. 47. Jacobsson L, Ottosson JO: Initial mental disorders in carCInoma of the pancreas and stomach. Acta Psychiatr Scand (suppt) 221:120-127.1971. 48 Wallen GOP. Connolly FH, Gittleson NL: A case of carcinoma of the pancreas with a psychiatric presentation. Br J Clln Pract 26:132-133,1972. 49. Arbitman R: Psychiatric manifeslations of carcinoma of the pancreas. Psychosomatics 13:269-271, 1972. 50. Luriia AR: Restoration 01 Function aller Brain tnjury. New York, Macmillan, 1963. 51. Report of Committee of Clinical Society of London: Nominated December 14, 1883 to investigate subjecl of myxoedema. Trans Clin Soc (London suppl) 21:14,1888. 52. Scholz T, Pfeiffer F: Roentgenologic diagnosis of carcinoma of the tail of the pancreas. JAMA 81 :275-277. 1923. 53. Fras I, Litin E, Pearson JS: Comparison of psychiatric symptoms in carcinoma of the pancreas with those In some other Inlraabdominal neoplasms. Am J Psychiarry 123:1153-1162,1967. 54. Weisman A, Worden JW: The existential plight in cancer. Significance of the first 100 days. IntJ Psychiatry Med 7:1-15, 1977. 55. Weisman AD: Early diagnosis of vulnerability in cancer patients. Am J Med Sci 271 :187196,1976 56. Abrams RD: Denial and depression In the terminal cancer patients-A clue tor management. Psychoanat 0 45:394-404.1971. 57. Greer S. Morris R, Pettingale KW: Psychological response to breast cancer: Effect on outcome. Lancet 1:785-787. 1979. 58. Hackett TP. Weisman AD: Denial as a factor in patients with heart disease and cancer. Ann NY Acad Sci 164:802-817, 1969. 59. Mcintosh J: Processes 01 communication, information seeking and control associated with cancer: A selective review of the literature.SocSciMed8:167-187.1974. 60. Holland JC, Rowland J, Plumb M: Psychological aspects of anorexia in cancer patients. Cancer Res 37:2425-2428,1977. 61. Shapiro WC: Remote effects of neoplasm on central nervous system: Encephalopathy, in Thompson RA. Green JR (eds): Advances in Neurology. New York, Raven Press, vol 15, 1976. 62. Peterson LG. Popkin MK: Neuropsychiatric effects of cancer chemotherapy agents. Psychosomatics 21:141-153,1980, 63. Schonfield J: PsyChOlogical facfors relafed to delayed return to an earlier life-style in successfully treated cancer palients. J Psychosam Res 16:41-46, 1972. 64. Ellinger L: Mortality and Morbidity alter Excessive Stress: A Follow-up tnvestigation of Norwegian ConcentratIon Camp Survivors. New York, Humanitaroan Press, 1973.
",._PA18140 793
Psychiatric aspects of cancer The authors review the psychiatric symptoms that may precede, accompany, and follow the onset of cancer. Difficulty in expressing anxiety, depression, or anger and low scores on these parameters in psychological testing along with depression and feelings of hopelessness are linked with the emergence of malignant tumors. Cancers of the brain, pancreas, and other endocrine organs, and hormone-secreting tumors frequently develop following the appearance of psychiatric symptoms. The psychological adjustment of cancer patients and the more common psychiatric sequelae of malignancy and its treatment are examined. The authors emphasize the need for careful assessment and attention to the biologic, psychological, and social factors critical to the patient's response and adjustment to the disease. stress were involved in the etiology of cancer.' Although, more recently, there have been accounts of spontaneous remissions of cancer attributed to personal faith as well as reports of rapidly accelerating malignancies in patients who have become depressed or suffered losses, an objective, systematic as-
sessment of the interaction of mental health and cancer is needed. The scientific community has long struggled with the intriguing possibility of cause and effect relationships between psychopathologic conditions and cancer. In fact, in 1966 the Annals of the New York Academy of Science devoted an entire issue to the topic.2 Unfortunately, 15 years later little clarification has emerged. Remaining unresolved is the role of psychological stress or psychiatric illness in the etiology of cancer. In this report, the available data on the relationship of psychopathology and cancer will be reviewed in terms of stages of malignancyprecancerous, early development, and the subsequent clinical course. Treatment and outcome will be considered with respect to the relationship between cancer and psychiatric illness.
Dr. Peterson is assistant prOfessor ofpsychiatry, University of Texas Medical School at Houston; Dr. Popkin is associate professor ofpsychiatry and medicine, University of Minnesota Medical School; and Dr. Hall is prOfessor ofpsychiatry and medicine, Medical College of Wisconsin, Milwaukee. Reprint requests to Dr. Peterson, PO Box 20708. 6431 Fannin, Houston, TX 77025.
Psychopathologic precursors to cancer The relationship between psychological stress and the development of cancer has interested physicians
ABSTRACT:
For centuries malignant tumors and mental health have been linked in the minds of both laymen and physicians. Galen observed that melancholic women seemed to develop cancer more frequently than sanguine women. In the 18th and 19th centuries, Guy, Paget, and Snow argued that depression and
(continued) 774
PSYCHOSOMATICS
Cancer: Psychiatric aspects
for many years. LeShan3 reviewed literature published between 1902 and 1957, which associated life stresses and psychiatric illness with the development of cancer. There were no controlled studies; the reports consisted of clinical vignettes. Depression, hopelessness, and grief emerged as frequently cited precursors of cancer. In 1976, Hurst 'and associates" reviewed studies from the late 1950s to the early 1970s linking depression and anxiety with the subsequent development of malignant tumors. In one prospective study, 1076 Johns Hopkins University medical students were observed for II to 27 years after initial psychological testing. The investigators found that nine subjects who later developed cancer had initially lower scores on depression, anxiety, and anger than those of students who subsequently developed mental illnesses and those of control subjects.5 In a ten-year follow-up study of 2550 Swedish citizens, Hagnell6 noted personality differences between persons who developed cancer and those who did not. He described the group developing cancer as "substable," showing more energy loss and withdrawal when depressed than their healthy counterparts. Since standard diagnostic nomenclature was not used in this study, it is difficult to compare with others. Kissen,7 Kissen and associates,8 and Abse and associates9 noted lower neuroticism scores on the Eysenck Personality Inventory by cancer patients, particularly those with lung cancer, than by other medical patients or normal control subjects. Patients in these studies were tested during hospitalizations for diagnostic evaluation. Accordingly, their Eysenck test scores
probably reflected preexisting personality patterns rather than sequelae of their illness. Studies by Huggan 'O in 1974 and by Greer and Morris " in 1975 on women with breast cancer demonstrate similar findings including extreme suppression of anger and, in elderly patients, suppression of other feelings as well. These observations differed from earlier research describing patterns of extraversion,'~ stress preceding the illness,1) and depression '4 in women with breast cancer. While these earlier studies
In human depressiollt increased cortisol levels and depressed function of T cells have been noted. usually included patients already diagnosed, Greer and Morris " evaluated 160 women just admitted for breast biopsies. Studies assessing affective state and life events proximate to the development of malignancy were done by LeShan and Worthington,15 Greene,16 and Bahnson and Bahnson. 17 Their findings all suggest that the loss of an intensely dependent relationship frequently occurs shortly before the clinical onset of cancer. Schmale and Iker '8 evaluated patients undergoing cone biopsies of the cervix. Based on the patients' reported feelings of hopelessness, the investigators made correct predictions of the biopsy results in more than two thirds of the cases. A similar study by Muslin and associates '9 did not identify recent loss as predictive of the outcome of breast biopsy in a series of 165 patients. The difference between loss (a life event) and hopelessness (a cognitive ap-
praisal of an event) may account for the disparity between the two studies. The discrepancy also might be related to the difference in the types of malignancy that were studied. Animal research by several groups shows that early traumatic experiences with rearing, the development of experimentally induced neurosis, and social stress may each impair immune response and increase vulnerability to the development and rapid spread of experimentally produced cancer.~o In human depression, increased cortisol levels and depressed function of T cells have been noted.21 Given the increased incidence of cancer in patients whose immune response has been suppressed for other reasons, it is possible that the immunosuppression associated with depression might be a mediating factor in cancer. Kerr and associates22 described a characteristic form of depressive illness that appeared to be a frequent precursor of cancer. Five of 28 males hospitalized with the diagnosis of depression later died of cancer. The number of deaths was greater than would be expected in an age-matched sample of the general population. All five men had depressive illness developing in middle age without apparent cause and without a history of psychiatric illness. The clinical picture was varied and included features of both reactive and endogenous depression. The immediate response to ECT and antidepressants was good, but transient. However, more extensive studies reviewing the incidence of malignancy in depressed patients have not confirmed the findings of Kerr and associates. Evans and associates23 reviewed the records of 823 patients hospi(conlin lied)
SEPTEMBER 1981 • VOL 22 • NO 9
779
Cancer: Psychiatric aspects
talized with a diagnosis of depression. In a four-year follow-up study, they found no increase in morbidity and mortality from malignancy. In Finland, Niemi and laaskelainen24 at ten- and 20-year intervals observed two groups of patients (N = 191) with the diagnosis, according to Feighner's criteria, of depressive illness. There was no significant increase in morbidity or mortality secondary to malignant disease. These two studies do not support the thesis that patients with depressive illness are at increased risk of developing cancer. Reports of hopelessness and depression immediately preceding a diagnosis of cancer may reflect a more general phenomenon of "giving up" which predates many medical illnesses, as discussed by EngelP Such a phenomenon might be explained by an underlying process causing both mood alteration and the clinical appearance of disease. This theory is supported by the increased incidence of psychiatric illness, especially affective, in patients with endocrine disturbances. Perhaps an internal feedback loop involving the immune, endocrine, and limbic systems contributes to the concurrent appearance of psychological and physical symptoms (see the Figure). The question of a relationship between depression and cancer is complicated by recent suggestions that psychotropic agents used to treat depression may contribute to an increased incidence of breast cancer.26 -28 Two subsequent studies, however, challenge this finding. 29 .3o The development of cancer has been thought to be inversely related to the development of schizophrenia. Rassidakis and associatesl ' noted a lower than expected SEPTEMBER 1981 • VOL 22 • NO 9
death rate from cancer among schizophrenic patients. They cited similar data in other European studies. Fox and Howell 32 suggested that this lower incidence may be ascribed to lifestyle differences between the general population and chronically hospitalized patients. Reports by Dynes33 and Ananth and Burnstein34 did not show a decreased incidence of malignancy among schizophrenic patients in the United States. At present, it seems premature to conclude that either schizophrenia or its treatment lowers the incidence of neoplastic disease. In conclusion, the data supporting specific connections betweeen psychiatric illness or psychological stress and the development of neoplastic disease are limited and largely retrospective. However, personality factors may be related to an increased incidence of malignancy in later life. Further, there appears to be a significant relationship between object loss, associated depression, and the clinical onset of at least some types of malignancy. Psychiatric presentations of cancer Reports of psychiatric symptoms in cancer patients have both theoretical and practical importance. Such
reports should heighten suspIcIon of malignancy in patients whose symptoms might otherwise be dismissed as functional. Understanding the mechanisms by which tumors of the central nervous system and endocrine glands, and other tumors produce psychiatric symptoms may, in turn, increase our understanding of the mechanisms underlying psychiatric illnesses currently thought to be functional. A careful review of the pertinent literature reveals numerous reports of patients with carcinomas of the pancreas who initially presented with psychiatric symptoms. In 1951 Soniat35 noted the association of psychiatric symptoms and intracranial neoplasms. More recently investigators have described psychiatric symptoms in patients with tumors of the endocrine system or with hormone-secreting tumors.36•40 Case reports and review articles in the last decade show increased attention to cancer patients who have behavioral abnormalities.40·41 But these studies often lack precise descriptions of the psychiatric symptoms, particularly those associated with organic mental disorders. Comments are usually limited to characterizations of mood state or grossly psychotic behavior. (continued)
Psychological stress
Physical stress
I
I
Affective response via limbic system
~
Immune response
Endocrine response (cortisol production)
FIG U RE-Hypothesizedfeedback loop involves the immune. endocrine, and limbic systems. 783
Cancer: Psychiatric aspects
The Table lists representative case reports of the last ten years.36.39 .42.49 In 37 case reports during that period, tumors of the central nervous system were preceded by psychiatric symptoms. Four of these were gliomas, five were cholesteatomas, and 20 were meningiomas. The interval from the observation of psychiatric symptoms to the subsequent diagnosis of the malignancy ranged from one to eight years. The psychiatric symptoms most commonly reported varied with the location of the tumor. Tumors of the spinal cord and brainstem most often were preceded by "conversion" symptoms. The earliest behavioral changes in patients with frontal lobe tumors included depression, apathy, and schizophreniform features. This range of psychiatric symptoms is comparable to that reported with frontal lobe disease generally.50 One patient found to have a tumor of the lateral ventricle initially had a psychosis including hallucinations, delusions, and pressured speech. Of the 37 case reports, a thorough neuropsychological evaluation of only eight patients was conducted. In each of these cases there was evidence of cognitive impairment accompanying mood and thought disturbances. Case reports in the last decade describing psychiatric presentations of endocrine and hormonesecreting tumors include 22 cases of carcinoid, one case of adenomatosis, and one of pheochromocytoma (see Table). Although reports associating psychiatric symptoms with thyroid dysfunction date back to 1888,51 no new reports of thyroid tumors with accompanying psychiatric symptoms were found in the literature of the last ten years. In the Table, the majority of patients 784
with tumors of the endocrine organs or with hormone-producing tumors had depression or anxiety. (The patient with adenomatosis exhibited aggression.) With the exception of a case of an ACTH-secreting oat cell carcinoma reported by Anderson and McHugh,36 there is no documentation of mental status findings or neuropsychological testing to distinguish organic mental disorders with affective symptoms from affective states with no known organic cause. In 1923 Scholz and Pfeffe~2 first described "nervousness" in patients preceding the diagnosis of carcinoma of the pancreas. In the last several years there have been two excellent articles addressing psychiatric issues in carcinoma of the pancreas. Fras and associates53
Weight loss and weakness were associated with all gastrointestinal tumors, but depression and irritability appeared to be linked only to carcinoma of the pancreas. in the United States and Jacobsson and Ottosson47 in Sweden both reviewed earlier literature and presented their own data. Jacobsson and Ottosson retrospectively determined the incidence of psychiatric symptoms in a series of patients with pancreatic carcinoma. Fras and associates53 evaluated newly diagnosed cases ofcarcinoma of the pancreas and other gastrointestinal tumors to determine the incidence and type of psychiatric symptoms. Of Jacobsson's and Ottosson's cases, 14% (8 of 57) had psychiatric symptoms, while 48% (22 of46) had psychiatric symptoms in Fras and associates' study. In both these and
other studies cited in the Table, psychiatric symptoms appeared from one to 43 months before the diagnosis of carcinoma. The most common constellation of symptoms included depression with weakness, irritability, and weight loss. Weight loss and weakness were associated with all gastrointestinal tumors, but depression and irritability appeared to be linked only to carcinoma of the pancreas. In Fras and associates' study, careful neuropsychological testing showed no evidence of organic mental disorder in any of the 46 patients. Psychiatric symptoms accompanying advanced cancer The incidence and nature of psychiatric symptoms among cancer patients have been discussed by Levine and associates.4o Depression appears to be the most frequently reported of these symptoms, cited in approximately 25% of patients. However, Plumb and Holland41 noted that this incidence is comparable to that among medical inpatients of all diagnoses. Organic mental disorders were present in 50% of the cases seen by Levine and associates.4o No other carefully documented series is available. Substantial psychological stress may be attendant on the diagnosis of cancer and on the subsequent physical ravages of the disease. Factors that may strongly influence psychological functioning include: (I) the reaction to the diagnosis by patient and family; (2) the patient's previous patterns of stress response (i.e., coping); (3) the direct effects of the cancer on the nervous system; (4) the indirect effects of cancer, especially alterations in metabolism; and (5) the effects of cancer treatment. The impact of the diagnosis inPSYCHOSOMATICS
Table-Cancer Preceded by Psychiatric Symptoms
Type of tumor
Loc8tIon of
Invedg8tor(a)
(N)
tumor
Burch at al42
Glioma (1)
Brain stem
Buchanan and Abrams43
Meningioma (1 )
Epstein et al 44
P.........nll psychlllllle aymptoma
Ment8I .......
Ut8nc1from
Of~
recognition 01 .....18IrIc 8f"IPI01H to
Iogleel tMIIng reported/OrpnIc mental symptoma mentioned
""1801
Conversion symptoms Hysterical neurosis
No/No
3}i yr
Lateral ventricle
Psychosis Pressured speech
Yes/Yes
<3wk
Multiple (27)
Spinal cord
Hysterical neurosis. conversion type
No/No
1-8 yr
Avery45
Meningioma (7)
Frontal lobe
Depression Apathy
Yes/Yes
4 wk-6 yr
Cole46
Oligodendroglioma (1)
Fron~al
Schizophrenia
No/Yes
6yr
Anderson and McHugh36
Oat cell carcinoma (1)
.Lung
Depression Suicide attempt
Yes/No
several days
Gilmer'l7
Pheochromocytoma (1)
Organs of Zuckerkandl
Depression
Yes/No
several days
Major et al38
Carcinoid (22)
Depression Anxiety
No/No
Not known
Carney et al39
Adenomatosis (1 )
Aggression
NoNes
None
Jacobsson and Ottosson 47
Pancreatic carcinoma (8).
Pancreas
Irritability Weakness Depression
No/No
6 wk-1% yr
Wallen et al 48
Pancreatic carcinoma (1)
Pancreas
Depression
No/No
2wk
Arbitman4g
Pancreatic carcinoma (1)
Pancreas
Depression Anxiety
No/No
10 mo
SEPTEMBER 1981 • VOL 22'
09
lobe
C8I1cer
785
................... ,.......
..,..t.,.~
...,
8efcIl-. prMCrIblng, ,..... conault comp1et8 product Infonn8tlon• • sumnwry of wtllCh follows: Indlc:etlons: Management of anxiety disorders. or short·term relief of symptoms ot anxiety. Anxiety or tension associated with the stress of ellllryday life usually does not require treatment with an anxiolytic Symp· tomatic reliet of acute agitation. tremor. impending or acute delirium tremens and hallucinosis due to acute alcohol withdrawal: ad;unctively in relief 01 skeletal muscle spasm due to reflex spasm to local pathology; spasticity caused by upper motor neuron disorders; athetosis; s@·man syndrome Oral form may be used adJunctlliely in convulsive disorders, but not as sole therapy Injectable form may also be used adJunctiliely In status epilepticus. sellere recurrent seizures. tetanus; anxiety. tension or acute stress reactions prior to endoscopic/surgical procedures; cardioversion The effectiveness 01 Valium (diazepam/Roche) In long.term use. that is. more than 4 months. has not been assessed by systematic clinical studies The phySician should periodically reassess the usefulness 01 the drug lor the individual patient eomqlncllC8tlona: Tablels in children under 6 months 01 age. known hypersensitivity. acute narrow angle glaucoma, may be used in patients with open angle glaucoma who are receiving appropnate therapy Wunlnga: As with most CNS·aCling drugs, caution against hazardous occupalions reQuinng complete mental alertness (e.g, operating machinery. driving) Withdrawal symptoms Similar to those With barbiturates and alcohol have been observed with abrupt discontinuation. usually limited to extended use and excessive doses InlreQuently, milder withdrawal symptoms have been reported 10llOWlng abrupt discontinuation 01 benzodiazeplnes after continuous use, generally at higher therapeutic lellels, tor at least several months After extended therapy, gradually taper dosage Keep addictlonprone Individuals (drug addicts or alcoholics) under caretul surveillance because of predisposition to habituation/dependence
UNge In PregrIency: U.. 01 minor tqnqullizers dUring flm trimester ahould almost alwsya be .wlded beceu.. oIln_ _ rlak 01 congennel malformetlona, .a auggntad In ..".,.1 stud.... eonaldal' posslblilty of pregnancy when Instituting therapy; advl. . patlenta to dlKuaa therapy If they Intand to or do becoma pregnant. ORAL Advise patients against simultaneous ingestion 01 alcohOl and other CNS depressants Not of value ,n treatment of psychotic patients. should not be employed In lieu 01 appropnate treatment When USing oral IorIO adlunctively in convulSive disorders, possibility 01 increase in IreQuency and/or seventy 01 grand mal seizures may reqUire Increase In dosage ot standard anticonvulsant medica· tion, abrupt Withdrawal in SUCh cases may be associated With temporary Increase in frequency and/or severity 01 seizures INJECTABLE To reduce fhe pOSSibility of venous thrombOSIS. phlebilis. local Iff/lalion. swellmg, and, rare/y, vascular Impalfmenr when used I V m/eCI slowly. takmg at leasl one minule for each 5 mg (I mlj given. do not use small vems. Ie. dorsum of hand or Wf/st, use extreme care to aVOid mtra-artef/al admlOistratlon or exlravasat,on Do nOI mix or dilule Valium with other solu· t,ons or drugs 10 syringe or mfuSlon lIask II it IS not feasible 10 adminisler Valium dlfectly / V.. It may be mjected slowly through the mfuSlon tubmg as close as possible 10 /he vein mser/IOn Administer With exlreme care to elderly. very ill. those With limited pulmonary reserlle because of poSSibility of apnea and/or cardiac arrest. concomitant use 01 barbiturates, alcohol or other CNS depressants increases depreSSion With Increased risk of apnea. have reSUSCitative lacilities available When used with narcotic analgeSIC eliminate or reduce narcotic dosage at least '!:l. administer in small increments Should not be administered to paMnts In shock, coma, acute alcoholic intOXication With depression of vital signs Has precipitated tonic status epilepticus In patients treated lor petit mal status or petit mal van ant status Not recommended for OB use Efficacy/salety not established In neonates (age 30 days or less); prolonged eNS depreSSion observed In children. give slowly (up to 0 25 109/kg over 3 minutes) to aVOid apnea or prOlonged somnolence, can be repeated after 15 to 30 mmutes If no reliel after third administration. appropnate adJunctive therapy IS recommended PNcautlona: If combined With other psychotroplCS or antlconvulsants. carefully conSider ,ndiVidual pharmacologic effects-particularly With known compounds which may potentiate action of Valium (diazepam/Roche), Ie. phenoth;azines. narcotics. barbiturates. MAO Inhibitors and antidepressants Protective measures indicated ,n highly anxIOUS patients With accompanYing depreSSion who may have SUICidal tendenCies Observe usual precautions In impaired hepatiC lunctlon; avoid accumulahon In patients with compromised kidney lunchon Limit oral dosage to smallest effective amount in elderly and debilitated to preClude ataxia or oversedat,on (Initially 2 to 2'1:1 109 once or twice dally. Increasing gradually as needed or toleraled) The clearance of Valium and certain other benzodiazeplnes can be delayed ,n association With Tagamet (Clmetidine) administration The clinical Significance of thiS is unclear INJECTABLE Although promptly controlled. seizures may return. re·administer if necessary. not recommended for long-term maintenance therapy Laryn· gospasm/increased cough reflex are POSSible dunng peroral endoscopic procedures, use topical anesthetiC. have necessary countermeasures available Hypotension or muscular weakness possible, particularly when used with narcotics, barbiturates or alcohOl Use lower doses (2 to 5 109) lor elderly/debilitated ~ Reactions: Side effects most commonly reported were drowsi· ness. fatigue. ataxia Infrequently encountered were confusion. constipation. depression. diplopia. dysarthria. headache. hypotension. incontinence. Jaundice. changes in libido. nausea. changes in salivation. skin rash. slurred speech. tremor. urinary retention, llertigo. blurred vision: Paradoxical reac· tions such as acute hyperexcited states. anxiety. hallUCinations. Increased muscle spasticity. insomnia. rage. sleep disturbances and stimulation have been reported, should Ihese occur. discontinue drug Because of isolated reports 01 neutropenia and Jaundice. periodic blOod counts. Iiller function tests advisable during long·term therapy. Minor changes in EEG patterns, usually low·voltage last activity. have been observed in patients during and after Valium (diazepam/Roche) therapy and are of no known significance INJECTABLE: Venous thrombOSIS/phlebitis at injection site. hypoactivity. syncope, bradycardia, cardiovascular collapse, nystagmus. urticana. hiccups. neutropenta In peroral endoscopic procedures. coughing. depressed respiration, dyspnea. hyperventilation. laryngospasm/pain in throat or chest have been reported. Management 01 o-doHga: Manifestations Include somnolence. confusion. coma. diminished reflexes Monttor resptrahon. pulse. blood pressure. employ general supportille measures. IV fluids. adequate airway. Use levarterenol or metaraminol lor hypotenSion DialySIS is of limited value.
®
ROCHE LABORATORIES
IIOCII •
DIVISIon of Holtmann-La Roche Inc Nuney. New Jersey 07110
Cancer: Psychiatric aspects
volves factual knowledge and fictional tradition. Both the astrological connection of cancer with the crab and the portrayal of cancer in stories such as "The Death of Ivan I1yitch" reinforce the dread of the disease. Scores of articles have discussed whether the physician should reveal the diagnosis to the patient and his family. In books as well as movies-the latter often based on successful books (e.g., Love Story, Death Be Not Proud, and Brian's Song)-patients struggle bravely against cancer. Weisman and Worden54 examined the adjustment of patients to cancer during the first 100 days of their illness. They found that psychosocial distress was more important in predicting the patient's ability to cope with cancer and its ramifications than the specific diagnosis or prognosis. In a companion project, Weisman55 found that patients with marital problems, a tendency to repress feelings, and a history of depression had the greatest difficulty coping with their illness. In three separate investigations of patients' responses to the diagnosis of cancer and its treatment, the presence and extent of denial of illness were associated with better psychological adjustment, decreased morbidity, and increased survival.5b.58 Weisman55 has also noted the importance of communication between spouses, and Mclntosh5~ has reviewed literature concerning communication processes and how they affect the patient's adjustment to cancer. Thus, the psychological state of the patient and the nature of the available social support systems affect both adjustment to the illness and the risk of morbidity and mortality. Conversely, cancer and its treatment may impinge on the pa788
PSYCHOSOMATICS
tient's psychological well-being. Anorexia and cachexia, associated with cancer, are likely to cause negative changes in body image and to compromise the capacity for physical pleasure.bo This is compounded by additional direct and indirect effects of cancer on the nervous system.61 Further, chemotherapy also produces complications affecting the central nervous system.62 In addition, the strain on interpersonal relations may have psychological repercussions. In the later stages of cancer, psychological problems are similar to
Psychosocial distress was more important in predicting the patient's ability to cope with cancer and its ramifications than the . specific diagnosis or prognosis. those of other patients approaching death. Responses, which are likely to reflect earlier patterns of coping with stress, may include anger, withdrawal, extreme dependency, ·denial, or'a combination. By knowing the patient's earlier coping styles (e.g., stress response) and un·derstanding his or her theological or . philosophical attitude toward 'death, the physician can intervene ,effectively with the patient in this phase of the illness and the family. Ironically, it is the patient who has a particularly long remission or , survives despite expectations to the contrary who often suffers the most · substantial psychosocial ill effects.bJ :This obserVation is consistent with accounts' of survivors of other se.vere emotional and' physical · stresses, such. as detention , . in a con,
c~ntration camp.64 The following case describes such a survivor.
Case report A 46-year-Old married woman was referred for psychiatric evaluation because of marital problems. Adenocarcinoma of the lung had been dicignosed two years earlier. The patient had not been expected to survive more than six months because of the advanced stage of the cancer at the time of its diagnosis. Four months later she had a spontaneous remission with considerable regression of the tumor. She and her husband stated that their marriage had been good until the preceding year. The patient complained that her husband was no longer interested in sharing activities with her and that he badgered her about painting the house and doing housework. He felt his wife was too demanding and that she had lost interest in him and their children. They reported that following the diagnosis of cancer, they had traveled extensively in the United States and Europe, trying to do as much as possible while the patient was still able to function. With the remission of the tumor, she had continued to spend more time than usual visiting friends around the country. Her husband preferred to settle back into their old routines at home, but he felt guilty about restricting his wife's activities since she did not have 16ng to live. Therap'y ended when the couple began to talk openly about the difficulty of treating the patient as any other family member rather than as a person with the entitlement reserved for the dying. ,Summary
Psychological traits that may make for a predisposition to the developImentofmalignancy includ~ limited expression of depression, anger, and anxiety; and a tendency to respond to stress with decreased energy and emotional withdrawal. Feelings of hopelessness or the loss .' of a significant relationship fre-
quently have been observed near the time of the diagnosis of cancer. Those cancers most likely to be preceded by psychiatric symptoms are brain tumors-particularly in the frontal, temporal, or parietal lobes-endocrine or hormone-secreting tumors, and tumors of the pancreas. The most prevalent psychiatric conditions accompanying malignancies are affective disorders or organic mental disorders. Once cancer has been diagnosed, the patient's adjustment will depend on previous patterns of coping with stress, the quality a':ld availability of, social support systems, the nature of the malignancy, and treatment. Appropriate assessment of the effects of psychological, social, and biologic factors on the person's adjustment is an important way of minimizing the morbidity and mortality of cancer. Support groups for patients and their families and early psychiatric consultation may reduce the risk of severe and intractable reactions to having cancer. Finally, even among those patients who are successfully treated, anxiety, loss of morale, and loss of a sense of well-being may hamper the return to a normal and satisfying life. 0 The authors wish to thank Ms. Sue' Wickham, Ms. Mindy Leifer, and Ms.' Terri Paddock for their invaluable help in the preparation ofthis manuscript. REFERENCES 1. Goldfarb C, Oriesen J, Cole 0: Psychophysi." ological aspects of malignancy. Am J Psychi· atry 123:1545-1552,1967.
2. Bahnson CB, Kissen OM: Psychophysiologi. , cal aspects of cancer. Ann NY Acad Sci
125:773-1055,1966. '.
.
3. LeShan L: Psychological states as factors in . the development of malignant disease: A crit-', ical review. J Nail Cancer Inst 22:1-18,1959.' 4. Hurst MW, Jenkins CD, Rose RM: The relation of psychological stress to onset of medical illness. Annu Rev Med 27:301-312, 1976. , .
e
,
" (continued) ,
SEPT,EMBER 1981· VOL 22' NO 9
789 .
,
TRANXENE~
(elorazepa'e dipotassium)@;
INDICATIONS - For manaoement of anxiety disorders or short-term relief of symptoms of anxiety: for symptomatic relief of acute alcohol withdrawal; for adjunctive therapy in partial seizures. Anxiety or tension associated with stress of everyday life usually does not require treatment with an anxiolytic. Effectiveness in long-term management ot anxiety (over 4 months) not assessed by systematic clinical studies. The physician should periodically reassess usefulness tor each patient. CONTRAlNOICATIONS - Known hypersensitivity to the drug. Acute narrow angle glaucoma. WARNINGS - Not for use in depressive neuroses or psychotic reactions. Caution patients against hazardous occupations requiring mental alertness, such as operating dangerous machinery including motor vehicles. Advise against simultaneous use of other CNS depressants, and caution patients lhat effects of alcohol may be increased. Not recommended for patients under 9. Nervousness, insomnia, irritability, diarrhea, muscle aches, and memory impairment have followed abrupt withdrawal from longterm high dosage. Withdrawal symptoms were reported after abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Use caution in patients having pyschological potential for drug dependence (dependence has been observed in dogs and rabbits).
Pregnancy and lactation: Minor trlnqulllzers should almOlt alnys be avoided IIrst trlmelter. Consider poalbility 01 pregnancy before Initiating tIlerapy. PatIent should consult pllyalcian about dlscontinua· tlon II aile becomes pregnant or plans pregnancy. Do not give to nursing mothers. PRECAUTIONS - Observe usual precautions in depression accompanying anxiety. or in patients with suicidal tendency. or those with impaired renal or hepatic function. 00 periodic blood counts and liver function tests during prolonged therapy. Use small doses and gradual increments in the elderly or debilitated. ADVERSE REACTIONS- Drowsiness. diuiness, various gj. complaints, nervousness. blurred vision, dry mouth, headache. mental contusion. insomnia, transient skin rashes. fatigue, ataxia. genitourinary complaints. irritability. diplopia. depression, slurred speech. abnormal liver and kidney function, decreased hematocrit, decreased systolic blood pressure. INTERACTIONS - Potentiation may occur with ethyl alcohol, hypnotics, barbiturates, narcotics, phenothiazines, MAO inhibitors. other antidepressants. In bioavailability stUdies with normal subjects, concurrent administration of antacids at therapeutic levels did not significantly influence bioavailability of TRANXENE. OVERDOSAGE - Take general measures as for any CNS depressant. SUPPLIED - TRANXENE 3.75.7.5. and t5 mg capsules and scored tablets. TRANXENE-SO Half Strength tl.25 and TRANXENE·SO 22.5 mg single dose tablets. REFERENCES:-l. Snyder SH: Anxiety: The Therapeutic Dilemma. No.2. Management Alternatives. Monograph 970544. 1981. P6-7.2. Sedation reported in normal volunteers 30 minutes after dosing. TRANXENE Drug Monograph 970185.1981. P9.3. Hollister lE: Anxiety: The Therapeutic Dilemma. No.2. Management Alternatives. Monograph 970544, 1981. P 11. 4. Mielke DH, Goethe JW: Anxiety: The Therapeutic Dilemma, No.2, Management Alternatives, Monograph 97-0544, 198t, P31.5. Elimination kinetics of an agent can be closely defined but cannot at present be related to therapeutic or adverse effects. 6. Hollister lE: op cit. p 13. 7. TRANXENE Drug Monograph 97-0185.1981. p 15.
EJ
Abbott Laboratorlesl Abbott Pharmaceuticals, Inc. North Chicago. IL 60064
Cancer: Psychiatric aspects
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792
22:117-120,1978. 25. Engel GL: A life seltlng conducive to illness: The giving-up-given-up complex. Ann Intern Med 69:293-299, 1968. 26. Boston Collaborative Drug Surveillance Program: Reserpine and breast cancer. Lancef 2:669-671, 1974 27. Armstrong B, Stevens N, Doll R: Retrospective study of the association between use of rauwolfia derivatives and breast cancer in English women. Lancet 2:627-675, 1974. 28. Heinonen OP, Shapiro S, Tuom,nen L: Reserpine use In relation to breast cancer. Lancet 2:675-677,1974. 29. Overall JE: Prior psychiatric treatment and the development of breast cancer. Arch Gen Psychiatry 35:898-899, 1978. 30. Laska EM, Siegel C, Meisner M, et al: Matched-pairs study of reserpine use and breast cancer. Lancet 2:296-300. 1975. 31. Rassidakis NO, KelepoUis M, Goulis K. et al: On the incidence ot malignancy among schizophrenic patients. Agressologie 14:259-273, 1973. 32. Rox BH, Howell MA: Cancer risk among psychiatric patients: A hypothesis. Int J Epidemio/3:207-208,1974.
33. Dynes JB: Cause of death in schizophrenia. Vir Med Monthly 96:338-340, 1969. 34. Ananth J, Burnstein M: Cancer: Less common in psychiatric patients? Psychosomatics 18:44-46,1977. 35. Soniat TlL: Psychiatric symptoms associated with Intracranial neoplasms. Am J Psychiatry 108:19-22,1951. 36. Anderson AE, McHugh RP: Oat cell carcinoma with hypercortisolemia presenting to a psychiatriC hospital as a suicide attempt. J NervMentDis 152:427-431, 1971. 37. Gilmer RE: Phaeochromocytoma-An interesting psychiatric presentation. S AIr Med J 46:174-176.1972. 38. Malor LF, Brown GL, Wilson WP: Carcinoid and psychiatric symptoms. South Med J 66787-790,1973. 39 Carney MWP, Jackson F, We,nbren I. ef al: Multiple adenomatosIs presenting with psychiatric manifestations. Postgrad Med J 47:242-243, 1971. 40. LeVine PM, Silberfarb PM, Lipowski ZJ: Mental disorders in cancer patients: A study of 100 psychiatric referrals. Cancer 42:12851291,1978 41. Plumb MM, Holland J: Comparative studies of psychological function in patients with advanced cancer. I. self-reported depressed symptoms. Psychosom Med 39:264-276. 1977 42 Burch EA. Hutch,son CF. Still CN: Hysterical symptoms masking brain stem glioma. J Clin Psycho/39:75-78.
43. Buchanan DC, Abram HS: Psychotic behavIor resulting from a lateral ventricle meningioma: A case report. Dis Nerv Syst 36:400401,1975 44. Epstein BS, Epstein JA. Poslel OM: Tumors of the spinal cord simulating psychiatric disorders. Dis Nerv Syst 32:741-743,1971. 45. Avery Tl: seven cases ot frootal tumour With
PSYCHOSOMATICS
psychiatric presenlation. Br J Psychiatry 119: 19-23. 1971. 46. Cole G: The masking of organic brain disease by a schizophrenia-like illness. S Afr Med J 47:731-733.1973. 47. Jacobsson L, Ottosson JO: Initial mental disorders in carCInoma of the pancreas and stomach. Acta Psychiatr Scand (suppt) 221:120-127.1971. 48 Wallen GOP. Connolly FH, Gittleson NL: A case of carcinoma of the pancreas with a psychiatric presentation. Br J Clln Pract 26:132-133,1972. 49. Arbitman R: Psychiatric manifeslations of carcinoma of the pancreas. Psychosomatics 13:269-271, 1972. 50. Luriia AR: Restoration 01 Function aller Brain tnjury. New York, Macmillan, 1963. 51. Report of Committee of Clinical Society of London: Nominated December 14, 1883 to investigate subjecl of myxoedema. Trans Clin Soc (London suppl) 21:14,1888. 52. Scholz T, Pfeiffer F: Roentgenologic diagnosis of carcinoma of the tail of the pancreas. JAMA 81 :275-277. 1923. 53. Fras I, Litin E, Pearson JS: Comparison of psychiatric symptoms in carcinoma of the pancreas with those In some other Inlraabdominal neoplasms. Am J Psychiarry 123:1153-1162,1967. 54. Weisman A, Worden JW: The existential plight in cancer. Significance of the first 100 days. IntJ Psychiatry Med 7:1-15, 1977. 55. Weisman AD: Early diagnosis of vulnerability in cancer patients. Am J Med Sci 271 :187196,1976 56. Abrams RD: Denial and depression In the terminal cancer patients-A clue tor management. Psychoanat 0 45:394-404.1971. 57. Greer S. Morris R, Pettingale KW: Psychological response to breast cancer: Effect on outcome. Lancet 1:785-787. 1979. 58. Hackett TP. Weisman AD: Denial as a factor in patients with heart disease and cancer. Ann NY Acad Sci 164:802-817, 1969. 59. Mcintosh J: Processes 01 communication, information seeking and control associated with cancer: A selective review of the literature.SocSciMed8:167-187.1974. 60. Holland JC, Rowland J, Plumb M: Psychological aspects of anorexia in cancer patients. Cancer Res 37:2425-2428,1977. 61. Shapiro WC: Remote effects of neoplasm on central nervous system: Encephalopathy, in Thompson RA. Green JR (eds): Advances in Neurology. New York, Raven Press, vol 15, 1976. 62. Peterson LG. Popkin MK: Neuropsychiatric effects of cancer chemotherapy agents. Psychosomatics 21:141-153,1980, 63. Schonfield J: PsyChOlogical facfors relafed to delayed return to an earlier life-style in successfully treated cancer palients. J Psychosam Res 16:41-46, 1972. 64. Ellinger L: Mortality and Morbidity alter Excessive Stress: A Follow-up tnvestigation of Norwegian ConcentratIon Camp Survivors. New York, Humanitaroan Press, 1973.
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