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Psychiatric Considerations in the Primary Medical Care of the Patient With Renal Failure
Psychiatric Considerations in the Primary Medical Care of the Patient With Renal Failure Norman B. Levy The adequate primary care of patients with renal failure, from the choice of the modality of treatment down to the everyday answering of questions of patients, relatives, and staff, requires a knowledge of the major psychological stresses of the illness and the psychiatric complications resulting from these stresses and their treatment. Among the major stresses of dialysis are the procedure itself, the overall medical treatment which includes medications and diet, and dependency·independence issues arising from the unique and almost abject dependency of patients on a machine, a procedure, and a group of medical professionals. As a result of these physical and psychological stresses, the disorders seen include delirium, depression, anxiety, suicide, uncooperative behavior, sexual dysfunctions, and psychosis. In their treatment, one should first consider what prophylactic steps should be taken to avoid their occurrence. It is best that a behaviorally trained professional be involved in the initial evaluation of all prospective patients. Ideally this should be a consultation-liaison psychiatrist. Such involvement may help in the selection of a modality of treatment best suited for the psychosocial background of the patient and help identify those most susceptible to psychiatric symptoms and disorders. Patients should be told of the possibility of complications such as sexual dysfunctions and, in the case of dialysis patients, that they may at some point in the course of their treatment consider voluntary withdrawal from it. Medications have an important role in the treatment of anxiety, insomnia, depression, psychosis, and sexual dysfunctions. Concerning the latter, behavioral techniques of Masters and Johnson have been found to be useful. Talking therapies seem to be of value for only to a limited number of motivated patients. © 2000 by the National Kidney Foundation, Inc. Index Words: Biopsychosocial; psychonephrology; depression; anxiety; delirium; sexual dysfunction.
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ithout adequate evaluation and accomodation for psychiatric factors the primary care of the patient with renal failure cannot meet a standard of good medical care. The reality is that virtually every primary care medical professional takes into consideration at some level the personality assets and liabilities of every patient in making decisions. Such decisions include the choice of modality of treatment of renal failure down to everyday relatively minor ones including the answering of questions of patients, family, and staff. Therefore, the better informed that medical professionals are concerning their patients' psychiatric stresses, complications, syndromes, and their treatment, the better they are able to make decisions, not soley based on "intuition" but rather on hard data and the experience of other medical professionals knowledgeable in this area of medical care. The net result should be better medical care and most probably better quality of life for their patients.
Stresses of Illness and Treatment Everybody knows the generally held and probably axiomatic view that the artificial organ, even the transplanted one, is never as good as
the original. Unfortunately, this is quite true of renal replacement therapies. The kidneys of people with normal renal function work flawlessly probably removing yet unidentified products of metabolism continually every second of every minute of every day. This cannot be said of forms of dialysis. Renal transplantation approaches normal kidney function but carries with it the baggage of immunosuppressant therapy and the probability of rejection some time in the future. The Dialysis Procedure The procedure of delivery of dialysis varies according to the modality of dialysis treatment. Using as a model in-center hemodialysis, we medical professionals accept as an
From the Department of Psychiatry and Medicine, State University of New York Health Science Center at Brooklyn, and Department of Psychiatry, Coney Island Hospital, Brooklyn, NY. Address correspondence to Norman B. Levy, MD, Director of Emergency Services, Department of Psychiatry, Coney Island Hospital, 2601 Ocean Parkway, Brooklyn, NY 11235; e-mail: [email protected]. © 2000 by the National KidnetJ Foundation, Inc. 1073-4449/00/0703-0006$3.00/0 doi: 10. I053/jarr.2000.8132
Advances in Renal Replacement Therapy, Vol 7, No 3 (July), 2000: pp 231-238
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everyday, "white noise" phenomenon of the dialysis procedure what in reality is a heroic form of treatment. It is important to keep in mind that for patients this is a treatment in which all of their blood leaves their body, goes into a complicated man-made contraption and returns to it, only to have the procedure repeated. Most have or will see in the dialysis center life and death situations involving other patients involved in blood loss and other serious events. In days past in which hemodialysis was a much longer procedure causing patients to receive treatment overnight, insomnia owing to anxiety was a common event. In those days we had the opportunity to deal with other phenomena connected with dialysis procedure anxiety, the most dramatic of which was that of masturbation among male patients. We saw this, not primarily as a sexual phenomenon but rather as what has been described in men about to enter battle in wartime, as a method of handling anxiety. The 2 forms of dialysis, peritoneal and hemodialysis, are sources of remarkably similar stresses and psychiatric complications. But there are some differences. The most prevalent form of peritoneal dialysis is chronic ambulatory peritoneal dialysis (CAPD), which shares with other self-care modalities of treatment advantages to the patient who has a very independent personality, the discussion of which follows a bit later. Peritoneal dialysis patients have a tube attached to their abdomen which connects to their peritoneal space. They also sustain in the course of their treatment repeated change in the girth of their abdomens. Although one might expect these changes in their bodies to be connected with significant psychological stress, it is remarkable how well almost all adapt to it.
The Medical Regimen Aside from the procedure of dialysis, the rest of the medical regimen takes an additional toll. Although many do not adhere to the letter of their diet, most attempt to, and some do so. This is a low-phosphate, low-potassium, lowsodium and, worst of all, a restricted-fluid intake diet. In addition, medications need to be taken. This may include many phosphate binding tablets daily. For the transplant patient the medication regimen is even more
critical, as immunosuppressants adequately taken in proper doses are essential to the life of the transplanted organ and to patients themselves. Dependency-Independency Issues Renal replacement therapy involves a highlyabnormal dependency situation. For the dialysis patient this includes abject dependency on a procedure, a group of medical professionals, and a medical regimen, surpassed in the past only by the use of the external respiratory for bulbar poliomyelitis. Such dependency places the very independent patient in an uncomfortable and even, in some cases, untenable situation. Therefore, the assessment of the independence of patients is essential in choosing the modality of renal replacement therapy. Most knowledgeable people in the field know that such independent patients should be in a form of self-care dialysis or transplanted. Unfortunately, very dependent patients may find the dependency of dialysis to satisfy their personality needs, thus making rehabilitation, including return to work, school, or full household activity less likely. For the transplant patient dependency-independency conflicts surround the importance of taking their medicines and returning periodically for blood tests and examinations.
Psychiatric Complications of Renal Replacement Therapies Delirium
Delirium is one of the most common complications of all medical and surgical treatments.! It is a syndrome caused by a deficiency in the delivery of adequate nutrients to the brain and by other deficiencies, which include failure of vital organs such as the heart, liver, and kidneys and in every syndrome of overproduction or underproduction of hormones. In addition, delirium can occur in toxic states caused by medicines and substances such as alcohol and street "medicines" and in states of electrolyte imbalance. Such a wide array of causes can potentially impact the patient in renal failure in a number of instances from inadequate dialysis treatment to failure of a transplanted kidney, post-dialysis disequilibrium, secondary and tertiary hyperparathyroidism
Psychiatric Considerations
and infections, just to mention a few possible causes of delirium. 2 It is more likely to occur in the elderly where it has been shown in different studies to have an incidence varying from 11 % to 45% among inpatients of all illnesses over the age of 65. The diagnosis of delirium can be made by the presence of 3 criteria. They are a relatively acute onset, a cognitive deficiency, and the presence of waxing and waning signs in a patient in whom there is a medical state in which delirium may occur. By cognitive, one means an intellectual disorder in which the patient may show evidence of disorientation, memory problems, and/or a state of relative consciousness impairment varying from slightly sleepiness to unconciousness. Characteristically, people who suffer from delirium tend to have an exaggeration of their premorbid personality so that the somewhat depressed may become clinically depressed, and the borderline may become overtly psychotic. As to the treatment of delirium, one must obviously deal with the underlying medical disorder and treat the manifesting symptoms. In transplant patients one needs to keep in mind the fact that virtually all immunosupressant medicines can cause delirium. Depression and Suicide Depression is the most common psychiatric complication of all medical illnesses, no less those associated with renal failure and replacement treatments. By depression one means something more than just a transient or even persistent mood but a syndrome present for more than hours or a few days associated with feeling of poor self esteem and possible ideas of or even suicidal action. A depressive syndrome usually has associated with it somatic concomitants such as an eating, sleeping, and/ or a sexual disorder. However, because renal failure and its treatments may already have the aforementioned somatic concomitants, the diagnosis of depression in patients with renal failure should best rely on depressive feelings including hopelessness, helplessness, poor worth, and suicidal thoughts. Along the latter lines it is essential that every medical professional working with renal patients keep in mind that there is a body of experience and research showing that suicide is much more common in dialysis patients than in the gen-
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eral population. 1 In understanding why some people become depressed, one may view depression as a response to loss, real, threatened or, in some cases, even speculated. People on renal replacement treatments have many possible real and threatened losses. Most do not return to their employment, which represents more than just a loss of money because work for most people is attached to their sense of self-esteem and even identity as a man or woman. There is often also a loss of a sense of freedom, loss of physical integrity, loss of sexuality, and loss of life expectancy. Depression can and should be treated vigorously, primarily with antidepressants, the discussion of which follows later. Anxiety Anxiety was undertaken in the previous section on the stress of the procedure of dialysis. Anxiety, certainly in lower animals and to a degree in our species, is a protective signal of impending danger. It may be experienced by patients at times in which their treatment and medical personnel are being changed, and in times in which tests are being performed and reported on, especially biopsies. A persistent or chronic anxiety may occur in renal transplant patients as a response to the fear of impending or inevitable rejection of the organ. This has been called the "Sword of Damocles Syndrome." The treatment of anxiety is primarily by the use of benzodiazepines, a discussion of which follows in the section on treatment. Non-Compliant Behavior Among the most vexing problems for renal medical professionals is maladaptive and noncompliant behavior of the transplant and dialysis patient. To more fully understand this phenomenon one must remember that in the United States mainly and in other countries to a much lesser extent, there has been a democratization of renal replacement therapy. By that term what is meant is that virtually everyone is now eligible for some form of renal replacement treatment. Although renal failure affects all strata of society, it favors those who are substance abusers, and diabetics and hypertensives who do not adhere to their medical regimen. Therefore, renal failure, although universal, is skewed in the direction
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of the patient who is less likely to be able to cooperate with the arduous medical regimen of dialysis and renal transplantation. In considering who is noncompliant, there is no issue concerning the extremes of behavior. However, what some medical professionals might consider as uncooperative might not be deemed so by patients. This may include the person who asks many questions, who doubts the recommendations made, and who seeks second opinions. Consumerism is more than just a word, it is also an integral and accepted part of being a patient, certainly in the United States and possibly in other countries as well. To the saying, "This above all, do no harm," one might add, "And do not permit harm to be done." Let me exemplify this by telling you the following: In a hemodialysis center in which I was a consultant, I was presented with the fact that a long-standing patient would routinely come into the unit and empty his pockets on the bedside table, which always included a large knife. The nurse presenting this to me said that she felt somewhat compromised by seeing the knife, even though the patient never attempted to use it or threatened to use it. This is an example, certainly not the worst, of unacceptable behavior on the part of the patient in which the staff deserves responsibility for not bringing this to the attention of the patient who might not have seen this as unacceptable. Staff members are often too passive of unacceptable behavior. Morally, ethically, and legally we have a responsibility to protect our staff and our patients. Such protection includes not permitting a patient to be dialyzed who presents an ongoing threat and, in extreme circumstances, calling the police and insisting that a patient be arrested. Too often, staff members overtolerate noncompliant and even criminal behavior. Another aspect of handing noncompliant behavior has to do with our setting unrealistic expectations of our patients, in which they may even join in. Renal professional personnel are, as a group, high attainers. It is only natural to tend to put our own set of values on others, despite our knowledge of the diversity of society. I can best exemplify this by saying that if one is religious and one feels that one has the
only real and best religion, one usually has difficulty accepting the fact that others do not see matters the same way. What I am saying is that in defining goals, one should individualize them and to the best of one's ability leave out personal ideals. Many years ago when I evaluated every patient considered for inclusion in a large hemodialysis center, one such candidate, although he had 8 years of education, was illiterate. My goal as well as that of the Director of the Center, was to educate the patient to become literate, not as a condition of dialysis, which could have been done in that day, but rather while being a dialysis patient. He too joined in this goal, which would relieve him of the embarassment of his illiteracy. What I forgot to take into consideration in making this man more like me was the fact that he came from more than just a deprived environment but also an abused background in which the same factors which hindered his educability as a child was operative then as a young adult. What happened was that he never was unable to keep appointments for classes and dropped out, much to our and his disappointment. By setting such an unrealistic goal, I did an injustice to this patient, who under other circumstances may have been erroneously viewed as uncooperative. The "take home" message here is that practical goals must be met realistically and individually. Such goals should not necessarily include in all patients the expectation that they will adhere to the medical regimen. Some people consciously or otherwise trade off longevity with dietary indiscretion and miss dialysis runs. Sexual Dysfunction Problems with sexual functions are relatively common in patients undergoing forms of renal replacement therapy, especially those undergoing dialysis. The possible exception now is the patient undergoing adequate daily dialyses. The earliest clinical observations were that many men receiving hemodialysis had difficulty getting and/ or maintaining an erection. There is now a small, significant body of research showing that men and women on forms of dialysis not just hemodialysis, have problems with sexual function. About 70% of men on dialysis have or develop partial or total impotence. Both men and women on
Psychiatric Considerations
dialysis have a marked degree of lessened sexual interest, termed libido. Women on dialysis have a sharp drop in the frequency that they experience orgasm during intercourse in comparison with that before renal failure. People of both genders who receive kidney transplants report improvement in sexual functions, but apparently a well functioning transplanted kidney does not return the patient to the degree of sexual function experienced before renal failure. The cause of sexual dysfunction of people on renal replacement therapies is not fully known. An attempt to incriminate hormonal dysfunction has not been fruitful. Research has shown that although psychiatric factors have a causal role, they do not explain sexual dysfunction in the majority of afflicted patients. We do know that among the psychiatric factors are those affecting one's sense of gender identity. A woman's sense of her feminity is put to the test in the cessation of menstruation, marked diminution in her fertility, discoloration of her skin caused by her somewhat uremic state, and scars of access surgery. In men, because the organ of urination is the same organ of sexuality, the virtual cessation of urination, by far the most common use of the penis, may cause a decreased sense of masculinity, especially in those whose perception of their masculinity was not great even before renal failure. Depression, the most common psychiatric complication, carries with it as one of its somatic complications a diminution in libidinal interest and function. Psychosis A flurry of interest arose in the mid 1970s when a report was published that hemodialysis cured a small number of schizophrenic patients who had normal renal function. Unfortunately, like many other premature announcements of its cure, this one also proved to be unfounded. The fact of the matter is that dialysis neither cures nor causes psychotic disorders, but, as previously mentioned, patients on forms of renal replacement treatment are prone to medical and surgical complications that may cause delirium. This is a syndrome which may have an organic psychosis associated with it.
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Miscellaneous Quality of Life Problems All the previously mentioned psychiatric complications of renal replacement therapies may greatly affect quality of life. In an attempt to be somewhat comprehensive, others should be mentioned. Sleep disorders are common in dialysis patients. Sleep apnea and painful neuropathy are the most common causes of this problem. Most patients on renal replacement therapies do not return to their employment, which in itself may cause a number of problems, not the least of which is a reduced family income. 3 In many households this may cause the wife of the renal failure patient to return to full-time outside work activity, placing the renal patient in the position of being a house-husband responsible for activities, which may have been largely the responsibility ot his wife. In many households this may work well, but for some men this may be perceived as an inroad on their masculinity. One should keep in mind the fact that renal failure greatly affects the family of the victim. Fatigue, diet, unemployment, periodic hospitalizations, visits to dialysis centers, outpatient appointments, and compromised longevity do not only affect the patient but also alter family dynamics. At a patients' organization meeting I was once confronted by a woman who said that the spouses of patients are the true unsung heroes of renal replacement therapies.
Therapies Preventions As previously mentioned, the evaluation of the independent needs of patients should be a major factor in determining the modality of treatment for renal failure. People who are very independent, not just pseudo-independent, should be placed in some form of selfcare or should be transplanted. Preliminary evaluation of patients should include that conducted by a professional who is trained in behavior medicine, preferably, but not necessarily, by a psychiatrist. The value of doing this is to identify early those individuals who suffer from psychiatric disorders including substance abuse, so that reasonable goals may be set for them and that they may be
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either treated and/ or monitored for their disorder. Although every physician knows that informed consent for treatment should always include telling the patient the possible complications associated with that treatment, my experience is that this is rarely performed for those consenting to dialysis. Future dialysis patients should be told about their likelihood of having sexual problems and suffering from depression. Aside from legal and moral reasons to inform these people of these psychiatric complications, the medical reason to do so is that it enhances their likelihood of calling these problems to the attention of staff and increases their opportunity to receive treatment for these problems. Psychiatric Active Medications Fortunately, almost all psychiatric active medications are fat soluble, pass the blood-brain barrier, are not dialyzable, are detoxified by the liver, and are excreted in the bile, not in the urine. 4 The "bad news" is that as a group they tend to be very protein-binding in people whose ability to bind protein is compromised. This means that in comparison with a person with normal renal function, a given dose of medicine will have a greater portion of it unbound and therefore available for potential toxicity. The rule of thumb is that patients with renal failure should receive no more than two thirds the maximum dose of medicine that a person with normal renal function should receive. In considering any and every medicine for use in people on forms of dialysis, one should pay attention to two issues: how is the medicine excreted, and is it dialyzable?4 Lithium carbonate is an exception to the above. It is a small, dialyzable molecule which does not bind with protein and which is exclusively excreted by the kidney. Essentially its two negatives in its potential use, dialyzability and excretion, can be used as advantages in the following way: The patient should be given a single dose after each dialysis run, which, in the presence of renal failure, will result in maintenance of a therapeutic drug level until the next dialysis, which will remove all of the drug. 4 The family of medicines known as the benzodiazepines are the major ones which
should be considered in the treatment of anxiety in these patients. They have great advantage over their predecessors, the barbituates. Benzodiazepines are the safest medications in the pharmacopoeia with a therapeutic/side effect ratio exceeding all others. Virtually, their sole side effect is over-sedation. They do not interact with other medicines, are not connected with allergic responses, do not cause rashes, and cannot be used as a method of suicide in a group of people with a high incidence of that method of demise. Perhaps best of all, they almost always work. The downside in their use is that patients tend to become habituated to them, and one must cautiously taper doses in removing their use, especially the shorter acting alprazolam (Xanax; Pharmacia-Upjohn Co, Penpack, NJ). Rapid withdrawal from alprazolam in a patient taking it for any reasonable period of time may be associated with a very symptomatic withdrawal syndrome, which may include grand mal seizures. Because depression is the most common psychiatric complication of dialysis, the use of anti-depressants should be part of the armamentarium of every nephrologist. There are several families of these medications. The most widely used are the selective seratonin reuptake inhibitors (SSRIs). Fluoxetine (Prozac; Eli Lilly & Co, Indianapolis, IN) is the SSRI that has been studied most in dialysis patients. 5 A pharmacokinetic study in which I was the principal investigator showed that single daily doses of 20 mg were metabolized similarly in depressed dialysis patients as in depressed subjects with normal kidney function. 6 All the SSRIs and other families of antidepressants may be used in patients on forms of renal replacement therapies. Some special attention might be paid to one of the family of tricyclic antidepressants, nortriptyline. Its use in patients in renal failure is enhanced by the fact that it is the only antidepressant in which blood levels are indicative of its potential efficacy. It has a therapeutic window of 50-150 ng/mL, above and below which it is not effective. As in the case of its fellow tricyclics, it is contraindicated in patients with cardiac conduction defects be-
Psychiatric Considerations
cause, in its in delaying cardiac conduction, an overdose may be fatal. Another major family of psychiatric active medications are the antipsychotics. These include such medicines as thorazine, haloperidol (Hal dol; Ortho-McNeil Pharmaceutical Corp, Raritan, NJ), risperidone (Risperdal; Janssen Pharmaceutica, Titusville, NJ), and olanzapine (Zyprexa; Eli Lilly & Co). They, as well as the mood stabilizers of which lithium had been a major player, now surpassed by the anticonvulsant valproic acid (Depakote, Depakene; Abbott Laboratories, Inc, North Chicago, IL), may be used in patients in renal failure subject to the previously mentioned rule of thumb. 4 Talking Psychotherapy It has been said that dialysis patients are the
greatest deniers of psychiatric problems. They share with people suffering from other medical and surgical illnesses the tendency to hide behind their illness and treatment. Perhaps the following statement captures what I mean. "If you had my illness, wouldn't you be depressed?" Of course, the fact of the matter is that, although clinical depression is common in these patients, the vast majority of patients do not suffer from it. Further, the antidepressants are about two-thirds effective in eleviating depression. Such patients are more likely to accept a medicine to help their anxiety or depression than attempt to find out why it arose. Thus, talking therapies are not common in these people. Group therapies have been used with varying success. The general rule for success in them is that the more educational they are, the more likely successful. Despite what has been previously said, the occasional patient may be successfully treated in individual psychotherapy and even psychoanalysis. Sexual Therapies A significant aggravating factor in those suffering from sexual dysfunctions is the tendency to withdraw altogether from sexuality, thereby adding further insult to their difficulties. Masters and Johnson formulated a treatment to reunite sexually divided couples in making love without necessarily having the expecta-
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tion of orgasmic release. This involves a progressive process of sensate focusing, stimulation, and enhancement of sexual confidence. For the male with impotence several techniques are available. The most recent has been the release of the medicine sidenafil (Viagra; Pfizer, Inc, New York, NY), which has a highefficacy profile which has overshadowed other medical and surgical techniques. Although there has been no systematic study of the use of sidenafil in these patients at the time of writing of this report, the clinical impression is that it is about 60% efficacious in doses varying between 25-100 mg. It is contraindicated in patients medicated by nitroglycerine or other medications which have coronary artery dilatation properties because the use of such medicines together with sidenafil have caused deaths owing hypotension. In those refractory to more conservative methods of treatment of impotence, surgical techniques include the insertion of a plastic rod into the body of the penis and the use of a hydrolic system of essentially pumping up the penis to the erect position. Voluntary Withdrawal From Renal Replacement Therapy One might question why such a topic is listed among the therapies. I have done so to underscore the fact that when such a decision, if properly made, not a product of a psychiatric disorder and adequately discussed with staff, family, and where appropriate with clergy and followed with proper palliative care, may be a reasonable way out of an intolerable situation? This area has been of considerable interest in recent years, in part because there is an increasing aging dialysis population in which the ravages of diabetes and other degenerative diseases are increasingly seen. Recent studies of those patients deciding to withdraw from treatment show that the overwhelming majority of them do not have major depressions or other psychiatric disorders and have not made suicide attempts in the past. Psychiatric consultants can be helpful in ruling out depressive and other emotional disorders. In every case attention should be paid to rendering palliative care so that the patient may have a good death. 8
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Conclusion An adequate knowledge of the stresses, psychiatric complications, and their treatment are essential for the proper and adequate primary medical care of patients on forms of renal replacement therapies.
References 1. Levy NB, Cohen LM: End-stage kidney disease and its treatment: Dialysis and transplantation, in Stoudemire A, Fogel BS, Greenberg 0 (eds): Psychiatric Care of the Medical Patient (ed 2). New York, NY, Oxford University Press, 2000, pp 791-799 2. Lipowski ZJ: Delirium: Acute Brain Failure, in Man. Springfield, IL, Charles C. Thomas, 388-389, 1980
3. Gutman RA, Stead WW, Robinson RR: Physical activity and employment status of p atients on maintenance dialysis. N Engl J Med 304:309-313, 1981 4. Levy NB: Psychopharmacology in patients with renal failure. Int J Psychiatry Med 20:303-312, 1990-1991 5. Blumenfield M, Levy NB, Spinowitz B, et al: Fluoxetine in depressed patients on dialysis. Int J Psychiatry Med 27:71-80, 1997 6. Levy NB, Blumenfield M, Beasley CM, et al: Fluoxetine in depressed subjects with renal failure and subjects with normal kidney function . Gen Hosp Psychiatry 18:8-13, 1996 7. Cohen LM, Fischel S, Germain M, et al: Ambivalence and dialysis discontinuation. Gen Hosp Psychiatry 18:431-435,1996 8. Cohen LM, McCue J, Germain M, et al: Dialysis discontinuation: A "good" death? Arch Intern Med 155:42-47, 1995
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ithout adequate evaluation and accomodation for psychiatric factors the primary care of the patient with renal failure cannot meet a standard of good medical care. The reality is that virtually every primary care medical professional takes into consideration at some level the personality assets and liabilities of every patient in making decisions. Such decisions include the choice of modality of treatment of renal failure down to everyday relatively minor ones including the answering of questions of patients, family, and staff. Therefore, the better informed that medical professionals are concerning their patients' psychiatric stresses, complications, syndromes, and their treatment, the better they are able to make decisions, not soley based on "intuition" but rather on hard data and the experience of other medical professionals knowledgeable in this area of medical care. The net result should be better medical care and most probably better quality of life for their patients.
Stresses of Illness and Treatment Everybody knows the generally held and probably axiomatic view that the artificial organ, even the transplanted one, is never as good as
the original. Unfortunately, this is quite true of renal replacement therapies. The kidneys of people with normal renal function work flawlessly probably removing yet unidentified products of metabolism continually every second of every minute of every day. This cannot be said of forms of dialysis. Renal transplantation approaches normal kidney function but carries with it the baggage of immunosuppressant therapy and the probability of rejection some time in the future. The Dialysis Procedure The procedure of delivery of dialysis varies according to the modality of dialysis treatment. Using as a model in-center hemodialysis, we medical professionals accept as an
From the Department of Psychiatry and Medicine, State University of New York Health Science Center at Brooklyn, and Department of Psychiatry, Coney Island Hospital, Brooklyn, NY. Address correspondence to Norman B. Levy, MD, Director of Emergency Services, Department of Psychiatry, Coney Island Hospital, 2601 Ocean Parkway, Brooklyn, NY 11235; e-mail: [email protected]. © 2000 by the National KidnetJ Foundation, Inc. 1073-4449/00/0703-0006$3.00/0 doi: 10. I053/jarr.2000.8132
Advances in Renal Replacement Therapy, Vol 7, No 3 (July), 2000: pp 231-238
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everyday, "white noise" phenomenon of the dialysis procedure what in reality is a heroic form of treatment. It is important to keep in mind that for patients this is a treatment in which all of their blood leaves their body, goes into a complicated man-made contraption and returns to it, only to have the procedure repeated. Most have or will see in the dialysis center life and death situations involving other patients involved in blood loss and other serious events. In days past in which hemodialysis was a much longer procedure causing patients to receive treatment overnight, insomnia owing to anxiety was a common event. In those days we had the opportunity to deal with other phenomena connected with dialysis procedure anxiety, the most dramatic of which was that of masturbation among male patients. We saw this, not primarily as a sexual phenomenon but rather as what has been described in men about to enter battle in wartime, as a method of handling anxiety. The 2 forms of dialysis, peritoneal and hemodialysis, are sources of remarkably similar stresses and psychiatric complications. But there are some differences. The most prevalent form of peritoneal dialysis is chronic ambulatory peritoneal dialysis (CAPD), which shares with other self-care modalities of treatment advantages to the patient who has a very independent personality, the discussion of which follows a bit later. Peritoneal dialysis patients have a tube attached to their abdomen which connects to their peritoneal space. They also sustain in the course of their treatment repeated change in the girth of their abdomens. Although one might expect these changes in their bodies to be connected with significant psychological stress, it is remarkable how well almost all adapt to it.
The Medical Regimen Aside from the procedure of dialysis, the rest of the medical regimen takes an additional toll. Although many do not adhere to the letter of their diet, most attempt to, and some do so. This is a low-phosphate, low-potassium, lowsodium and, worst of all, a restricted-fluid intake diet. In addition, medications need to be taken. This may include many phosphate binding tablets daily. For the transplant patient the medication regimen is even more
critical, as immunosuppressants adequately taken in proper doses are essential to the life of the transplanted organ and to patients themselves. Dependency-Independency Issues Renal replacement therapy involves a highlyabnormal dependency situation. For the dialysis patient this includes abject dependency on a procedure, a group of medical professionals, and a medical regimen, surpassed in the past only by the use of the external respiratory for bulbar poliomyelitis. Such dependency places the very independent patient in an uncomfortable and even, in some cases, untenable situation. Therefore, the assessment of the independence of patients is essential in choosing the modality of renal replacement therapy. Most knowledgeable people in the field know that such independent patients should be in a form of self-care dialysis or transplanted. Unfortunately, very dependent patients may find the dependency of dialysis to satisfy their personality needs, thus making rehabilitation, including return to work, school, or full household activity less likely. For the transplant patient dependency-independency conflicts surround the importance of taking their medicines and returning periodically for blood tests and examinations.
Psychiatric Complications of Renal Replacement Therapies Delirium
Delirium is one of the most common complications of all medical and surgical treatments.! It is a syndrome caused by a deficiency in the delivery of adequate nutrients to the brain and by other deficiencies, which include failure of vital organs such as the heart, liver, and kidneys and in every syndrome of overproduction or underproduction of hormones. In addition, delirium can occur in toxic states caused by medicines and substances such as alcohol and street "medicines" and in states of electrolyte imbalance. Such a wide array of causes can potentially impact the patient in renal failure in a number of instances from inadequate dialysis treatment to failure of a transplanted kidney, post-dialysis disequilibrium, secondary and tertiary hyperparathyroidism
Psychiatric Considerations
and infections, just to mention a few possible causes of delirium. 2 It is more likely to occur in the elderly where it has been shown in different studies to have an incidence varying from 11 % to 45% among inpatients of all illnesses over the age of 65. The diagnosis of delirium can be made by the presence of 3 criteria. They are a relatively acute onset, a cognitive deficiency, and the presence of waxing and waning signs in a patient in whom there is a medical state in which delirium may occur. By cognitive, one means an intellectual disorder in which the patient may show evidence of disorientation, memory problems, and/or a state of relative consciousness impairment varying from slightly sleepiness to unconciousness. Characteristically, people who suffer from delirium tend to have an exaggeration of their premorbid personality so that the somewhat depressed may become clinically depressed, and the borderline may become overtly psychotic. As to the treatment of delirium, one must obviously deal with the underlying medical disorder and treat the manifesting symptoms. In transplant patients one needs to keep in mind the fact that virtually all immunosupressant medicines can cause delirium. Depression and Suicide Depression is the most common psychiatric complication of all medical illnesses, no less those associated with renal failure and replacement treatments. By depression one means something more than just a transient or even persistent mood but a syndrome present for more than hours or a few days associated with feeling of poor self esteem and possible ideas of or even suicidal action. A depressive syndrome usually has associated with it somatic concomitants such as an eating, sleeping, and/ or a sexual disorder. However, because renal failure and its treatments may already have the aforementioned somatic concomitants, the diagnosis of depression in patients with renal failure should best rely on depressive feelings including hopelessness, helplessness, poor worth, and suicidal thoughts. Along the latter lines it is essential that every medical professional working with renal patients keep in mind that there is a body of experience and research showing that suicide is much more common in dialysis patients than in the gen-
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eral population. 1 In understanding why some people become depressed, one may view depression as a response to loss, real, threatened or, in some cases, even speculated. People on renal replacement treatments have many possible real and threatened losses. Most do not return to their employment, which represents more than just a loss of money because work for most people is attached to their sense of self-esteem and even identity as a man or woman. There is often also a loss of a sense of freedom, loss of physical integrity, loss of sexuality, and loss of life expectancy. Depression can and should be treated vigorously, primarily with antidepressants, the discussion of which follows later. Anxiety Anxiety was undertaken in the previous section on the stress of the procedure of dialysis. Anxiety, certainly in lower animals and to a degree in our species, is a protective signal of impending danger. It may be experienced by patients at times in which their treatment and medical personnel are being changed, and in times in which tests are being performed and reported on, especially biopsies. A persistent or chronic anxiety may occur in renal transplant patients as a response to the fear of impending or inevitable rejection of the organ. This has been called the "Sword of Damocles Syndrome." The treatment of anxiety is primarily by the use of benzodiazepines, a discussion of which follows in the section on treatment. Non-Compliant Behavior Among the most vexing problems for renal medical professionals is maladaptive and noncompliant behavior of the transplant and dialysis patient. To more fully understand this phenomenon one must remember that in the United States mainly and in other countries to a much lesser extent, there has been a democratization of renal replacement therapy. By that term what is meant is that virtually everyone is now eligible for some form of renal replacement treatment. Although renal failure affects all strata of society, it favors those who are substance abusers, and diabetics and hypertensives who do not adhere to their medical regimen. Therefore, renal failure, although universal, is skewed in the direction
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of the patient who is less likely to be able to cooperate with the arduous medical regimen of dialysis and renal transplantation. In considering who is noncompliant, there is no issue concerning the extremes of behavior. However, what some medical professionals might consider as uncooperative might not be deemed so by patients. This may include the person who asks many questions, who doubts the recommendations made, and who seeks second opinions. Consumerism is more than just a word, it is also an integral and accepted part of being a patient, certainly in the United States and possibly in other countries as well. To the saying, "This above all, do no harm," one might add, "And do not permit harm to be done." Let me exemplify this by telling you the following: In a hemodialysis center in which I was a consultant, I was presented with the fact that a long-standing patient would routinely come into the unit and empty his pockets on the bedside table, which always included a large knife. The nurse presenting this to me said that she felt somewhat compromised by seeing the knife, even though the patient never attempted to use it or threatened to use it. This is an example, certainly not the worst, of unacceptable behavior on the part of the patient in which the staff deserves responsibility for not bringing this to the attention of the patient who might not have seen this as unacceptable. Staff members are often too passive of unacceptable behavior. Morally, ethically, and legally we have a responsibility to protect our staff and our patients. Such protection includes not permitting a patient to be dialyzed who presents an ongoing threat and, in extreme circumstances, calling the police and insisting that a patient be arrested. Too often, staff members overtolerate noncompliant and even criminal behavior. Another aspect of handing noncompliant behavior has to do with our setting unrealistic expectations of our patients, in which they may even join in. Renal professional personnel are, as a group, high attainers. It is only natural to tend to put our own set of values on others, despite our knowledge of the diversity of society. I can best exemplify this by saying that if one is religious and one feels that one has the
only real and best religion, one usually has difficulty accepting the fact that others do not see matters the same way. What I am saying is that in defining goals, one should individualize them and to the best of one's ability leave out personal ideals. Many years ago when I evaluated every patient considered for inclusion in a large hemodialysis center, one such candidate, although he had 8 years of education, was illiterate. My goal as well as that of the Director of the Center, was to educate the patient to become literate, not as a condition of dialysis, which could have been done in that day, but rather while being a dialysis patient. He too joined in this goal, which would relieve him of the embarassment of his illiteracy. What I forgot to take into consideration in making this man more like me was the fact that he came from more than just a deprived environment but also an abused background in which the same factors which hindered his educability as a child was operative then as a young adult. What happened was that he never was unable to keep appointments for classes and dropped out, much to our and his disappointment. By setting such an unrealistic goal, I did an injustice to this patient, who under other circumstances may have been erroneously viewed as uncooperative. The "take home" message here is that practical goals must be met realistically and individually. Such goals should not necessarily include in all patients the expectation that they will adhere to the medical regimen. Some people consciously or otherwise trade off longevity with dietary indiscretion and miss dialysis runs. Sexual Dysfunction Problems with sexual functions are relatively common in patients undergoing forms of renal replacement therapy, especially those undergoing dialysis. The possible exception now is the patient undergoing adequate daily dialyses. The earliest clinical observations were that many men receiving hemodialysis had difficulty getting and/ or maintaining an erection. There is now a small, significant body of research showing that men and women on forms of dialysis not just hemodialysis, have problems with sexual function. About 70% of men on dialysis have or develop partial or total impotence. Both men and women on
Psychiatric Considerations
dialysis have a marked degree of lessened sexual interest, termed libido. Women on dialysis have a sharp drop in the frequency that they experience orgasm during intercourse in comparison with that before renal failure. People of both genders who receive kidney transplants report improvement in sexual functions, but apparently a well functioning transplanted kidney does not return the patient to the degree of sexual function experienced before renal failure. The cause of sexual dysfunction of people on renal replacement therapies is not fully known. An attempt to incriminate hormonal dysfunction has not been fruitful. Research has shown that although psychiatric factors have a causal role, they do not explain sexual dysfunction in the majority of afflicted patients. We do know that among the psychiatric factors are those affecting one's sense of gender identity. A woman's sense of her feminity is put to the test in the cessation of menstruation, marked diminution in her fertility, discoloration of her skin caused by her somewhat uremic state, and scars of access surgery. In men, because the organ of urination is the same organ of sexuality, the virtual cessation of urination, by far the most common use of the penis, may cause a decreased sense of masculinity, especially in those whose perception of their masculinity was not great even before renal failure. Depression, the most common psychiatric complication, carries with it as one of its somatic complications a diminution in libidinal interest and function. Psychosis A flurry of interest arose in the mid 1970s when a report was published that hemodialysis cured a small number of schizophrenic patients who had normal renal function. Unfortunately, like many other premature announcements of its cure, this one also proved to be unfounded. The fact of the matter is that dialysis neither cures nor causes psychotic disorders, but, as previously mentioned, patients on forms of renal replacement treatment are prone to medical and surgical complications that may cause delirium. This is a syndrome which may have an organic psychosis associated with it.
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Miscellaneous Quality of Life Problems All the previously mentioned psychiatric complications of renal replacement therapies may greatly affect quality of life. In an attempt to be somewhat comprehensive, others should be mentioned. Sleep disorders are common in dialysis patients. Sleep apnea and painful neuropathy are the most common causes of this problem. Most patients on renal replacement therapies do not return to their employment, which in itself may cause a number of problems, not the least of which is a reduced family income. 3 In many households this may cause the wife of the renal failure patient to return to full-time outside work activity, placing the renal patient in the position of being a house-husband responsible for activities, which may have been largely the responsibility ot his wife. In many households this may work well, but for some men this may be perceived as an inroad on their masculinity. One should keep in mind the fact that renal failure greatly affects the family of the victim. Fatigue, diet, unemployment, periodic hospitalizations, visits to dialysis centers, outpatient appointments, and compromised longevity do not only affect the patient but also alter family dynamics. At a patients' organization meeting I was once confronted by a woman who said that the spouses of patients are the true unsung heroes of renal replacement therapies.
Therapies Preventions As previously mentioned, the evaluation of the independent needs of patients should be a major factor in determining the modality of treatment for renal failure. People who are very independent, not just pseudo-independent, should be placed in some form of selfcare or should be transplanted. Preliminary evaluation of patients should include that conducted by a professional who is trained in behavior medicine, preferably, but not necessarily, by a psychiatrist. The value of doing this is to identify early those individuals who suffer from psychiatric disorders including substance abuse, so that reasonable goals may be set for them and that they may be
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either treated and/ or monitored for their disorder. Although every physician knows that informed consent for treatment should always include telling the patient the possible complications associated with that treatment, my experience is that this is rarely performed for those consenting to dialysis. Future dialysis patients should be told about their likelihood of having sexual problems and suffering from depression. Aside from legal and moral reasons to inform these people of these psychiatric complications, the medical reason to do so is that it enhances their likelihood of calling these problems to the attention of staff and increases their opportunity to receive treatment for these problems. Psychiatric Active Medications Fortunately, almost all psychiatric active medications are fat soluble, pass the blood-brain barrier, are not dialyzable, are detoxified by the liver, and are excreted in the bile, not in the urine. 4 The "bad news" is that as a group they tend to be very protein-binding in people whose ability to bind protein is compromised. This means that in comparison with a person with normal renal function, a given dose of medicine will have a greater portion of it unbound and therefore available for potential toxicity. The rule of thumb is that patients with renal failure should receive no more than two thirds the maximum dose of medicine that a person with normal renal function should receive. In considering any and every medicine for use in people on forms of dialysis, one should pay attention to two issues: how is the medicine excreted, and is it dialyzable?4 Lithium carbonate is an exception to the above. It is a small, dialyzable molecule which does not bind with protein and which is exclusively excreted by the kidney. Essentially its two negatives in its potential use, dialyzability and excretion, can be used as advantages in the following way: The patient should be given a single dose after each dialysis run, which, in the presence of renal failure, will result in maintenance of a therapeutic drug level until the next dialysis, which will remove all of the drug. 4 The family of medicines known as the benzodiazepines are the major ones which
should be considered in the treatment of anxiety in these patients. They have great advantage over their predecessors, the barbituates. Benzodiazepines are the safest medications in the pharmacopoeia with a therapeutic/side effect ratio exceeding all others. Virtually, their sole side effect is over-sedation. They do not interact with other medicines, are not connected with allergic responses, do not cause rashes, and cannot be used as a method of suicide in a group of people with a high incidence of that method of demise. Perhaps best of all, they almost always work. The downside in their use is that patients tend to become habituated to them, and one must cautiously taper doses in removing their use, especially the shorter acting alprazolam (Xanax; Pharmacia-Upjohn Co, Penpack, NJ). Rapid withdrawal from alprazolam in a patient taking it for any reasonable period of time may be associated with a very symptomatic withdrawal syndrome, which may include grand mal seizures. Because depression is the most common psychiatric complication of dialysis, the use of anti-depressants should be part of the armamentarium of every nephrologist. There are several families of these medications. The most widely used are the selective seratonin reuptake inhibitors (SSRIs). Fluoxetine (Prozac; Eli Lilly & Co, Indianapolis, IN) is the SSRI that has been studied most in dialysis patients. 5 A pharmacokinetic study in which I was the principal investigator showed that single daily doses of 20 mg were metabolized similarly in depressed dialysis patients as in depressed subjects with normal kidney function. 6 All the SSRIs and other families of antidepressants may be used in patients on forms of renal replacement therapies. Some special attention might be paid to one of the family of tricyclic antidepressants, nortriptyline. Its use in patients in renal failure is enhanced by the fact that it is the only antidepressant in which blood levels are indicative of its potential efficacy. It has a therapeutic window of 50-150 ng/mL, above and below which it is not effective. As in the case of its fellow tricyclics, it is contraindicated in patients with cardiac conduction defects be-
Psychiatric Considerations
cause, in its in delaying cardiac conduction, an overdose may be fatal. Another major family of psychiatric active medications are the antipsychotics. These include such medicines as thorazine, haloperidol (Hal dol; Ortho-McNeil Pharmaceutical Corp, Raritan, NJ), risperidone (Risperdal; Janssen Pharmaceutica, Titusville, NJ), and olanzapine (Zyprexa; Eli Lilly & Co). They, as well as the mood stabilizers of which lithium had been a major player, now surpassed by the anticonvulsant valproic acid (Depakote, Depakene; Abbott Laboratories, Inc, North Chicago, IL), may be used in patients in renal failure subject to the previously mentioned rule of thumb. 4 Talking Psychotherapy It has been said that dialysis patients are the
greatest deniers of psychiatric problems. They share with people suffering from other medical and surgical illnesses the tendency to hide behind their illness and treatment. Perhaps the following statement captures what I mean. "If you had my illness, wouldn't you be depressed?" Of course, the fact of the matter is that, although clinical depression is common in these patients, the vast majority of patients do not suffer from it. Further, the antidepressants are about two-thirds effective in eleviating depression. Such patients are more likely to accept a medicine to help their anxiety or depression than attempt to find out why it arose. Thus, talking therapies are not common in these people. Group therapies have been used with varying success. The general rule for success in them is that the more educational they are, the more likely successful. Despite what has been previously said, the occasional patient may be successfully treated in individual psychotherapy and even psychoanalysis. Sexual Therapies A significant aggravating factor in those suffering from sexual dysfunctions is the tendency to withdraw altogether from sexuality, thereby adding further insult to their difficulties. Masters and Johnson formulated a treatment to reunite sexually divided couples in making love without necessarily having the expecta-
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tion of orgasmic release. This involves a progressive process of sensate focusing, stimulation, and enhancement of sexual confidence. For the male with impotence several techniques are available. The most recent has been the release of the medicine sidenafil (Viagra; Pfizer, Inc, New York, NY), which has a highefficacy profile which has overshadowed other medical and surgical techniques. Although there has been no systematic study of the use of sidenafil in these patients at the time of writing of this report, the clinical impression is that it is about 60% efficacious in doses varying between 25-100 mg. It is contraindicated in patients medicated by nitroglycerine or other medications which have coronary artery dilatation properties because the use of such medicines together with sidenafil have caused deaths owing hypotension. In those refractory to more conservative methods of treatment of impotence, surgical techniques include the insertion of a plastic rod into the body of the penis and the use of a hydrolic system of essentially pumping up the penis to the erect position. Voluntary Withdrawal From Renal Replacement Therapy One might question why such a topic is listed among the therapies. I have done so to underscore the fact that when such a decision, if properly made, not a product of a psychiatric disorder and adequately discussed with staff, family, and where appropriate with clergy and followed with proper palliative care, may be a reasonable way out of an intolerable situation? This area has been of considerable interest in recent years, in part because there is an increasing aging dialysis population in which the ravages of diabetes and other degenerative diseases are increasingly seen. Recent studies of those patients deciding to withdraw from treatment show that the overwhelming majority of them do not have major depressions or other psychiatric disorders and have not made suicide attempts in the past. Psychiatric consultants can be helpful in ruling out depressive and other emotional disorders. In every case attention should be paid to rendering palliative care so that the patient may have a good death. 8
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Conclusion An adequate knowledge of the stresses, psychiatric complications, and their treatment are essential for the proper and adequate primary medical care of patients on forms of renal replacement therapies.
References 1. Levy NB, Cohen LM: End-stage kidney disease and its treatment: Dialysis and transplantation, in Stoudemire A, Fogel BS, Greenberg 0 (eds): Psychiatric Care of the Medical Patient (ed 2). New York, NY, Oxford University Press, 2000, pp 791-799 2. Lipowski ZJ: Delirium: Acute Brain Failure, in Man. Springfield, IL, Charles C. Thomas, 388-389, 1980
3. Gutman RA, Stead WW, Robinson RR: Physical activity and employment status of p atients on maintenance dialysis. N Engl J Med 304:309-313, 1981 4. Levy NB: Psychopharmacology in patients with renal failure. Int J Psychiatry Med 20:303-312, 1990-1991 5. Blumenfield M, Levy NB, Spinowitz B, et al: Fluoxetine in depressed patients on dialysis. Int J Psychiatry Med 27:71-80, 1997 6. Levy NB, Blumenfield M, Beasley CM, et al: Fluoxetine in depressed subjects with renal failure and subjects with normal kidney function . Gen Hosp Psychiatry 18:8-13, 1996 7. Cohen LM, Fischel S, Germain M, et al: Ambivalence and dialysis discontinuation. Gen Hosp Psychiatry 18:431-435,1996 8. Cohen LM, McCue J, Germain M, et al: Dialysis discontinuation: A "good" death? Arch Intern Med 155:42-47, 1995