Andrea DiMartini, MD

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Here: A summary of indicators for stress and anxiety in patients undergoing transplantation, and why it is important for psychiatrists to be aware of these factors.

Key Stressors in Transplant Psychiatry

Academy of Psychosomatic Medicine (APM), Transplant Psychiatry Special Interest Group

Because of the inherent risks and costs associated with transplant in addition to limited organ availability, careful candidate selection is crucial for successful outcomes. Given the prevalence and effects of psychiatric and substance use disorders on quality of life and post-transplant outcomes, the psychiatrist is often called upon to recommend or implement treatment in both pre-transplant and post-transplant stages.

, the various phases of transplant as well as the prevalence and impact of psychiatric illness in the transplant population were discussed.

 Here we review the psychiatric management of transplant patients and the evaluation and care of living organ donors.

It is important that preexisting psychiatric conditions are addressed while patients are being evaluated for or are awaiting transplant. In most cases, the early phase of the pre-transplant stage is an optimal time to “fine-tune” mental health treatment. The underlying medical condition is relatively stable, and the patient can still participate in psychotherapy or receive psychopharmacological treatment.

The hope for better quality of life after transplant can motivate patients to pursue mental health treatments that they had previously refused (eg, start addiction treatment, taper off sedatives, participate in psychotherapy). During this phase, mental health care follows the recommendations available for the psychiatric care of the medically ill.

In addition to general psychosomatic care, specific treatments such as transplant-focused stress-reduction interventions can be useful.

 As medical illness worsens, additional challenges may interfere with psychiatric care:

• Patients may become too physically ill to participate in mental health treatment.

• Cognitive impairment may prevent meaningful psychotherapy.

• The logistics of intense medical care (hospitalizations for medical decompensations, high number of medical appointments) may interfere with adherence to psychiatric treatment.

In the acute post-operative setting, psychiatrists are often asked to help diagnose and manage delirium and steroid-induced psychiatric symptoms. Post-transplant delirium is approached by systematic evaluation of risk factors; addressing acute medical conditions that contribute to delirium (such as infection and metabolic disturbances); simplification of the medication regimen whenever possible (eg, reducing dosages of opioids or benzodiazepines); and behavioral interventions (such as minimizing stimulation, promoting access to daylight normalization of sleep-wake cycle, early mobilization, and frequent reorientation). If medications are used, antipsychotics remain the first line of treatment. Antipsychotics can be safely used to treat delirium or steroid-induced psychosis in the post-transplant phase, while patients are monitored carefully for elevated QTc, seizures, hyponatremia, and neutropenia.

Psychotherapy can be implemented as stand-alone treatment or in addition to pharmacology.

In the long term, several studies have documented that depression or psychosis in the post-transplant phase is associated with worse medical outcomes.

 For substance use disorder, findings suggest that post-transplant treatment is as important as pre-transplant relapse prevention in helping patients maintain abstinence.

 General considerations regarding pharmacological treatment of organ transplant recipients are outlined in 

. The life-long immunosuppressant regimen may lead to psychiatric symptoms, pharmacokinetic interactions with psychiatric medications, or synergistic effects that can alter long-term outcomes (

Psychotherapy can be implemented as stand-alone treatment or in addition to pharmacology, provided there is no significant cognitive impairment. Relevant themes for psychotherapy in the post-transplant setting are loss (of time spent ill waiting for an organ, of social status, financial situation); change in social role (from critically ill to quasi-healthy); acceptance of the post-transplant limitations because of medical comorbidities not improved with the transplant (eg, diabetic retinopathy after a kidney transplant); guilt; body image concerns; living with an increased risk of health problems (malignancies, infections); medication adherence; and expressing gratitude toward the donor or his or her family. Many transplantation centers offer counseling focused on improving medication adherence and communicating with the donor or the donor’s family.

Evaluation and management of living organ donors

In addition to caring for patients who undergo transplant, psychiatrists are also asked to evaluate potential living organ donors. This primarily involves those who seek to donate a kidney or a portion of their liver. Donors may be closely related to the potential recipient, such as family or friends (“related donor”), but they can also be peripherally related, such as a co-worker (“unrelated directed donation”), or even someone who is unknown to the recipient and donates anonymously (“non-directed donation”).

Organ donors are carefully screened and at times require adjustments of their psychiatric care before being accepted as donors.

No matter what the nature of the relationship to the recipient, donor evaluations are similar to a pre-transplant candidate evaluation. However, there is greater emphasis on informed consent and determining whether there is coercion, undue psychological pressure, or otherwise unhealthy motivations driving the desire to donate (eg, enhancing self-worth, creating a relationship with the recipient, financial remuneration; 

Organ donors are carefully screened and at times require adjustments of their psychiatric care before being accepted as donors. An innovative, transplant-specific use of motivation enhancement therapy in living organ donors who express ambivalence about donating may reduce post-surgical physical and psychiatric symptoms.

Depression is the most common problem in organ donors. The cumulative rate of diagnosed depression in kidney donors was 4.2% at 1 year and 11.5% at 5 years, which is lower than in the general population.

 There is limited information on organ donors with preexisting psychiatric disorders; a small study of 22 kidney donors suggests that organ donation is not followed by psychiatric decompensation.

After donation, as organ function is recovering, psychotropic medications must be adjusted accordingly. Beyond the recovery period, it is wise to avoid psychotropic medications with direct toxicity (eg, lithium for kidney donors), although there is no clear evidence of a higher risk of toxicity in organ donors compared with the general population.

Transplant is the optimal treatment for a variety of advanced organ diseases. However, due in large part to the scarcity of available organs, transplant programs must carefully select patients who are most likely to benefit from this procedure.

Organs from living donors help address the gap between the need for and the supply of organs. Because these donors undergo surgery for no personal medical benefit, they must be carefully selected and monitored to minimize their risks.

Psychiatrists play a vital role as team members involved in the selection and care of transplant candidates, recipients, and living donors. Historically, their role has focused on the pre-transplant and perioperative phases of care. However, as the populations of long-term transplant survivors and living donors grow, psychiatrists are likely to be called on more often to provide recommendations, referrals, and care for both recipients and donors.

As the field of transplantation continues to expand, psychiatrists have greater responsibilities for the psychosocial evaluation of transplant and donor candidates, and for ensuring that transplant candidates understand the risks and benefits of deceased donor options and the possibility of living donation.

Post-transplant care of recipients also continues to evolve, with ongoing developments in immunosuppressant options. The neuropsychiatric adverse effects of these medications require careful study, especially during long-term use. Psychiatrists and other mental health professionals play vital roles in documenting the nature of these effects, and in determining whether and when patients need to switch to other therapies.

As the populations of long-term transplant survivors and living donors grow, psychiatrists are likely to be called on more often to provide care.

Novel strategies for behavior interventions also require additional research because transplant recipients often live far from their transplant centers. Effective interventions may need to be offered via telephone or the Internet, rather than through traditional face-to-face encounters.

Finally, new areas of transplantation are evolving, most notably transplant of vascularized composite allografts, including face, limb, and reproductive organ transplants.

 The mental health of individuals who are considered for these types of transplants can be one of the key indicators of need or justification for transplant. For example, the stigma associated with severe, permanent facial injury and disfigurement can be extreme and can lead to profound psychological distress.

Overall, the field of transplantation, as a whole, provides an abundance of opportunities for the psychiatrist as both clinician and researcher to contribute to the knowledge base and to the ongoing care and well-being of individuals undergoing extraordinary treatments.

The authors acknowledge Christina Wichman, DO, FAPM, of the Academy of Psychosomatic Medicine (APM) for helping bring this article to fruition. The APM is the professional home for psychiatrists providing collaborative care bridging physical and mental health. Over 1200 members offer psychiatric treatment in general medical hospitals, primary care, and outpatient medical settings for patients with comorbid medical conditions.

Dr. Zimbrean is Assistant Professor of Psychiatry and Surgery, Director of Transplant Psychiatry Services, and Associate Director of Psychosomatic Medicine Fellowship at Yale New Haven Hospital, New Haven, CT. Dr. Crone is Vice Chair, Department of Psychiatry, Inova Fairfax Hospital, Associate Professor of Psychiatry, George Washington University Medical Center, Washington, DC, and Immediate Past President, Academy of Psychosomatic Medicine. Dr. Sher is Assistant Professor of Psychiatry and Behavioral Sciences at Stanford University and Associate Director of Psychosomatic Medicine Fellowship at Stanford University Medical Center, Stanford, CA. Dr. Dew is Professor of Psychiatry, Psychology, Epidemiology, Biostatistics, and Clinical and Translational Science and Dr. DiMartini is Professor of Psychiatry and Surgery and Associate Professor of Clinical and Translational Science in the Department of Psychiatry at the University of Pittsburgh, Pittsburgh, PA. The authors report no conflicts of interest concerning the subject matter of this article.

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Articles

The authors focus on the psychiatric management of transplant recipients and the evaluation and care of living organ donors. 

Transplant Psychiatry: Psychiatric Care of Organ Donors and Recipients

Organ transplantation is the accepted treatment for many patients with chronic or acute advanced organ disease and certain types of cancer. Currently, there are over 120,000 patients in the US waiting for solid organ transplant (nearly 100,000 are kidney transplant candidates), and the wait list continues to grow. However, because of the shortage of donated organs, only about 30,000 transplants are performed each year and 10% to 18% of candidates will not survive to transplant. Most wait a year or more for a donated organ, while many kidney candidates wait 3 to 5 years.

Most organ transplant programs recognize the need for a multidisciplinary team to assist with the complexities of transplant patient care. Moreover, the United Network for Organ Sharing recognizes that “mental health and social support services are essential for the total care of transplant recipients, living donors and their families” and thus requires the availability of such services by trained individuals.

 Historically, psychiatrists and mental health professionals contributed primarily during the pretransplant evaluation phase, assisting transplant teams in determining the suitability of candidates for transplant and preparing candidates for the procedure.

Over the past 3 decades, the increasing numbers of candidates and recipients as well as the expansion of organ transplantation to more than 500 programs in the US have both increased the demand for mental health services within transplant programs and fostered the development of a specialized area of transplant psychiatry. Psychiatrists are increasingly considered integral members of the transplant team and are often embedded within the transplant units and clinics to provide continuity of psychiatric care.

The limited organ availability; extensive health care resources required; and degree of personal responsibility, self-management, and strict adherence to transplant directives needed of transplant recipients for successful outcomes necessitate careful candidate selection. Psychiatrists evaluate the extent to which psychiatric, psychological, and behavioral disorders may contribute to poorer outcomes and assist in designing treatment plans to ameliorate identified risks.

Following transplant, psychiatrists may be consulted on psychiatric or behavioral issues as they arise during the recovery period. Innovative strategies for dealing with these complex patients have been developed, including the adaptation of common therapeutic strategies specifically for transplant-related scenarios.

Organ transplant is not a singular surgical event but a series of transitions between specific phases beginning with the diagnosis of advanced organ disease. From referral to the transplant team to long-term adaptation to life as a transplant recipient, each phase is associated with different stressors that require different skills and resources from patients, their family and friend caregivers, and the mental health clinicians who care for them. The 

 illustrates the potential medical and psychosocial stresses inherent in each phase for patients and their caregivers.

The pre-transplant phase is commonly associated with anxiety over being evaluated and accepted onto the transplant wait list. Many patients and their families initially experience elation and relief over being listed but then find the uncertainty of waiting for an organ to be the most psychologically stressful part of the transplant experience. Those who have been chronically ill may look forward to transplant with its potential to improve their quality of life, while those who became acutely ill may view transplant with apprehension. Patients can experience a slow decompensation or rapid progression from acute exacerbations. Wait-list patients can experience medical events (eg, infection, stroke, myocardial infarction) that may make them ineligible for transplant.

While maintaining hope, patients and families may need to prepare for significant deterioration or death. Patients and caregivers must have adequate resources to adapt to the patient’s changing status and needs, including loss of role functioning, medical care and therapies, loss of physical functioning, and requiring assistance with activities of daily living. Families may experience financial hardships related to the cost of medical care, loss of the patient’s employment, or loss of the caregiver’s work time and wages.

In the early phase following transplant, patients often experience elation over surviving to receive an organ. Patients may expect the transplant will quickly restore their original health and quality of life. However, the realizations of post-transplant care and recovery can lead to frustration and discouragement. Not only is the post-transplant regimen complex, but patients may have become deconditioned and may require significant physical rehabilitation to achieve better functioning. They may have persistent cognitive deficits due to previous organ disease or post-transplant immunosuppressant medications.

Post-transplant complications or setbacks can lead to significant demoralization in some patients. Patients can develop psychological issues related to transplant-even PTSD related to the transplant experience-or they may have an exacerbation of an existing psychiatric disorder. Caregiver assistance is essential at this time until the recipient can function independently.

Over the long term, transplant typically improves but does not fully restore quality of life. Patients may feel chronically ill, develop new health problems, or experience various degrees of physical or cognitive impairments. Despite these potential issues, they may also experience pressure to return to work or other responsibilities. They may have financial difficulties, especially with health care costs. They also must deal with potential long-term sequelae of transplant, including the adverse effects of immunosuppression. Long-term complications are not inconsequential. For example, within 5 years, 15% to 20% of non-renal recipients have advanced renal failure due to post-transplant immunosuppression.

The role of the psychiatrist in transplantation

Psychiatrists play a significant role in the evaluation and care of organ transplant candidates and living organ donors-before and after transplant. The psychiatrist often functions as a transplant team member who assists in candidate evaluations and selection and provides direct care to patients awaiting transplant, as well as those in the perioperative or longer post-transplant phases. In other cases, teams may utilize a psychiatrist as a consultant to assist in these tasks.

The aims of the pretransplant psychiatric evaluation are summarized in the 

. The main goal is to determine whether there are psychiatric or psychological factors that may interfere with the patient’s ability to cope with the demands of the transplant. Substance use disorders, mood and anxiety disorders, and neurocognitive impairment are common in this population.

Although transplant teams may look to the psychiatrist as a “gatekeeper” or “detective” who will weed out candidates at high risk for poor outcomes, the psychiatrist should aim at enhancing patient candidacy whenever possible. This may require recommending formal addictions treatment, 12-step groups, psychotherapy, medications, neuropsychological testing, or referral to mental health providers in the community.

If a patient is receiving mental health care outside of the transplant center, the psychiatrist assists by providing communication, education, and care coordination between the team and outside provider or facility. When significant character pathology is present, the psychiatrist may help the transplant team develop coordinated approaches to reduce regressed behavior, such as splitting, that adversely affects the provision of effective medical care.

To facilitate the candidate evaluation, transplant-specific structured psychosocial assessment tools have been developed that can aid in a more standardized, uniform evaluation of psychosocial risk factors. These tools include Transplant Evaluation Rating Scale (TERS), Psychosocial Assessment of Candidates for Transplantation (PACT), and Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT).

 However, their value in predicting post-transplant outcomes is still under investigation.

Prevalence and impact of psychiatric illness in the transplant population

To accomplish the aims of the evaluation described above, the psychiatrist must be familiar with the prevalence of psychiatric presentations in transplant patients and with their impact on medical outcomes and quality of life. Patients with advanced medical illnesses that lead to transplant have increased rates of depression and anxiety. For example, 25% of patients with heart disease have MDD at some point in their lives

; 19% and 32% of adult patients with cystic fibrosis have elevated depression and anxiety symptoms, respectively

; and 37% of patients with chronic kidney disease report depression.

Depression and anxiety may continue after transplant. One study found that 58% of lung transplant recipients and 47% of heart transplant recipients experienced mood or anxiety disorders within the first 2 years after transplant; moreover, these disorders were frequently comorbid.

 In particular, 26% to 30% of these patients experienced MDD, 15% experienced PTSD related to the transplant, 14% to 22 % had adjustment disorder with anxiety, and 8% to 18% had panic disorder.

Depression can lower the quality of life and adversely affect medical outcomes after transplant. In a meta-analysis of 27 studies that included heart, liver, kidney, lung, and pancreas recipients (N = 53,158), depression was found to increase the relative risk of mortality by 65%.

 In addition, depression (but not anxiety) has been associated with increased death-censored graft loss in kidney recipients.

In a more recent study of lung transplant recipients, early post-transplant depression was associated with bronchiolitis obliterans syndrome, graft loss, and mortality.

 Evidence suggests that treatment of depression in recipients might improve post-transplant survival.

Cognitive disorders are also common in transplant populations, including pre-transplant, immediate post-transplant, and long-term post-transplant. It is important for psychiatrists to evaluate cognitive functioning in transplant candidates. Not only can impaired cognition have significant ramifications for the informed consent process, it might also make it more challenging for patients to care for themselves and follow their complex medical regimens, and it places a greater burden on their support system. Transplant candidates are at risk for cognitive impairment because of either an underlying disease process or comorbid neurovascular complications. For example, 47% of lung recipients had cognitive impairment before transplant.

 A high prevalence of cognitive impairment has been reported in patients with liver cirrhosis and in those with end-stage kidney disease.

In the immediate post-transplant period, acute cognitive impairment can occur as a part of delirium or can be induced by medications. Delirium has been reported in 37% to 73% of lung transplant recipients and 10% of liver recipients.

 Delirium is associated with increased mortality in liver transplant recipients, and prolonged intensive care unit and hospital stays in liver and lung transplant recipients.

A rare (1% to 2% of transplant recipients) but serious neurotoxic complication of immunosuppressive medications is the posterior reversible encephalopathy syndrome (PRES), which can cause delirium and/or a wide variety of neurological symptoms. Corticosteroids, necessary in high doses immediately after transplant, may induce psychosis, mania, anxiety, or insomnia.

Cognitive impairment may also persist into the post-transplant period. A large majority (80%) of lung transplant recipients with prior neurocognitive impairment remain impaired at 3-month follow-up, and new cognitive impairment develops in 70% of liver recipients by 1 year after transplant.

 Immunosuppressant medications may also contribute to new or persistent neurocognitive impairment after transplant.

Some patients require organ transplant because of disease related to alcohol, tobacco, or illicit drug use. End-stage liver disease due to hepatitis C, which is frequently contracted via intravenous drug use, and alcoholic liver disease account for over 60% of liver transplants.

 Chronic obstructive pulmonary disease, associated with tobacco use, leads to approximately one-third of all lung transplants.

While 1- and 5-year survival rates are more favorable in patients with alcohol-related liver disease than in recipients whose liver transplant resulted from other causes, the 10-year survival is worse in those who relapse on alcohol.

 Most programs have a mandatory 6-month abstinence rule prior to listing; however, this particular duration of sobriety has not been strongly validated in the literature. Some patients need longer sobriety and rehabilitation to significantly reduce their risk of relapse. On the other hand, if carefully selected, patients with fulminant alcoholic hepatitis who do not have time to maintain sobriety can have good posttransplant outcomes.

Interestingly, a large meta-analysis of mostly liver transplant patients did not demonstrate that alcohol relapse in this patient population is associated with noncompliance.

 However, relapse is associated with an increased risk of cancer and cardiovascular disease.

 A large study of patients with end-stage renal failure found tobacco, alcohol, or drug use up to the time of diagnosis was associated with a small but significant increased risk of graft loss.

 Tobacco use in renal recipients is associated with higher rates of various cancers, cardiovascular disease, graft loss, and death.

 Involvement of the psychiatrist in treatment planning and delivery may decrease relapse after transplant, especially if there is continuity of addiction treatment care.

Patient with serious mental illness (eg, bipolar disorder, psychotic disorders) are underrepresented in transplantation. There is limited evidence that these patients have poorer outcomes or are less adherent to directives. However, careful selection, expert management, good social support, and a collaborative relationship with the transplant team can ensure that even complicated patients have good posttransplant outcomes.

We have reviewed the various phases of transplant-from pre-transplant to post-transplant. There is an increased prevalence of psychiatric presentations in transplant patients; thus, psychiatrists with their unique knowledge are integral members of the transplant team from pre-transplant through post-transplant and beyond.

In the second part of this article, to be published in the October issue, we will discuss the psychiatric management of transplant patients and the evaluation and care of living organ donors.

Dr. Zimbrean is Assistant Professor of Psychiatry and Surgery, Director of Transplant Psychiatry Services, and Associate Director of Psychosomatic Medicine Fellowship at Yale New Haven Hospital, New Haven, CT. Dr. Crone is Vice Chair, Department of Psychiatry, Inova Fairfax Hospital, Associate Professor of Psychiatry, George Washington University Medical Center, Washington, DC, and Immediate Past President, Academy of Psychosomatic Medicine. Dr. Sher is Assistant Professor of Psychiatry and Behavioral Sciences at Stanford University and Associate Director of Psychosomatic Medicine Fellowship at Stanford University Medical Center, Stanford, CA. Dr. Dew is Professor of Psychiatry, Psychology, Epidemiology, Biostatistics, and Clinical and Translational Science, and Dr. DiMartini is Professor of Psychiatry and Surgery and Associate Professor of Clinical and Translational Science in the Department of Psychiatry at the University of Pittsburgh, Pittsburgh, PA. The authors report no conflicts of interest concerning the subject matter of this article.

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https://optn.transplant.hrsa.gov/media/1201/optn_bylaws.pdf#nameddest=Appendix_D

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 2nd ed. Vol 3. Oxford, UK: Academic Press (Elsevier); 2007:35-44.

Psychiatrists are playing an ever-increasing role in the evaluation and care of organ transplant candidates and living organ donors-before and after transplant.

Andrea DiMartini, MD

Articles

Key Stressors in Transplant Psychiatry

Transplant Psychiatry: Psychiatric Care of Organ Donors and Recipients

Transplant Psychiatry: An Introduction, Part 1