Catherine Crone, MD

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Beyond psychosocial implications of anxiety disorders, an array of physiological effects may ensue. 

7 Medical Illnesses That May Present as Anxiety

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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 Ramirez P, Febrero B, Martinez-Alarcon L, et al. Benefits of group psychotherapy in cirrhotic patients on the liver transplant waiting list.

 Dew MA, Rosenberger EM, Myaskovsky L, et al. Depression and anxiety as risk factors for morbidity and mortality after organ transplantation: a systematic review and meta-analysis. 

 Abbott KC, Agodoa LY, O’Malley PG. Hospitalized psychoses after renal transplantation in the United States: incidence, risk factors, and prognosis. 

 Rodrigue JR, Hanto DW, Curry MP. Substance abuse treatment and its association with relapse to alcohol use after liver transplantation. 

 Dew MA, DiMartini AF, DeVito Dabbs AJ, et al. Preventive intervention for living donor psychosocial outcomes: feasibility and efficacy in a randomized controlled trial.

 Lentine KL, Schnitzler MA, Xiao H, et al. Depression diagnoses after living kidney donation: linking U.S. Registry data and administrative claims. 

 Rowley AA, Hong BA, Martin S, et al. Psychiatric disorders: are they an absolute contraindication to living donation? 

 Jowsey-Gregoire SG, Morelon E, Petruzzo P, Seulin C. The Chauvet 2014 meeting report: psychiatric and psychosocial evaluation and outcomes of upper extremity grafted patients. 

 Naderi N, Bakhshandeh H, Ardeshiri M, et al. Hyper-prolactinemia in men with idiopathic dilated cardiomyopathy: does it have any prognostic implications? 

 Foley KF, Kast RE. Review of evidence that posttransplantation psychiatric treatment commonly affects prolactin levels and thereby influences graft fate. 

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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.

 Organ Procurement and Transplantation Network (OPTN) Bylaws. Appendix D: Membership Requirements for Transplant Hospitals and Transplant Programs. 2015. 

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

 Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. 

 Gazdag G, Horvath GG, Makara M, et al. Predictive value of psychosocial assessment for the mortality of patients waiting for liver transplantation.

 Carnrike Jr CL, McCracken LM, Aikens JE. Social desirability, perceived stress, and PACT ratings in lung transplant candidates: a preliminary investigation. 

 Maldonado JR, Sher Y, Lolak S, et al. The Stanford Integrated Psychosocial Assessment for Transplantation: a prospective study of medical and psychosocial outcomes. 

 Sher Y, Lolak S, Maldonado JR. The impact of depression in heart disease. 

 Quittner AL, Goldbeck L, Abbott J, et al. Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries. 

 Tsai YC, Chiu YW, Hung CC, et al. Association of symptoms of depression with progression of CKD. 

 Dew MA, DiMartini AF, DeVito Dabbs AJ, et al. Onset and risk factors for anxiety and depression during the first 2 years after lung transplantation. 

 Rosenberger EM, DiMartini AF, DeVito Dabbs AJ, et al. Psychiatric predictors of long-term transplant-related outcomes in lung transplant recipients. 

 Rogal SS, Dew MA, Fontes P, DiMartini AF. Early treatment of depressive symptoms and long-term survival after liver transplantation. 

 Smith PJ, Rivelli S, Waters A, et al. Neurocognitive changes after lung transplantation. 

 Lee Y, Kim C, Suk KT, et al. Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis. 

 Torres RV, Elias MF, Seliger S, et al. Risk for cognitive impairment across 22 measures of cognitive ability in early-stage chronic kidney disease. 

 Craven JL. Postoperative organic mental syndromes in lung transplant recipients. 

 Smith PJ, Rivelli SK, Waters AM, et al. Delirium affects length of hospital stay after lung transplantation. 

 Lescot T, Karvellas CJ, Chaudhury P, et al. Postoperative delirium in the intensive care unit predicts worse outcomes in liver transplant recipients. 

 Tryc AB, Pflugrad H, Goldbecker A, et al. New-onset cognitive dysfunction impairs the quality of life in patients after liver transplantation. 

 DiMartini A, Crone C, Dew MA. Alcohol and substance use in liver transplant patients. 

 Parker R, Armstrong MJ, Corbett C, et al. Alcohol and substance abuse in solid-organ transplant recipients. 

 Choudhary NS, Kumar N, Saigal S, et al. Liver transplantation for alcohol-related liver disease. 

 Dew MA, DiMartini AF, Steel J, et al. Meta-analysis of risk for relapse to substance use after transplantation of the liver or other solid organs. 

 Agarwal PK, Hellemons ME, Zelle DM, et al. Smoking is a risk factor for graft failure and mortality after renal transplantation. 

 Opelz G, Dohler B. Influence of current and previous smoking on cancer and mortality after kidney transplantation. 

 Dew MA, DiMartini A, Kormos RL. The stress of organ transplantation. In: Fink G, ed. 

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

Transplant Psychiatry: An Introduction, Part 1

Anxiety is a fundamental aspect of the human experience. It can be an adaptive response to a perceived threat, with both psychological and physiological features. In the short term, anxiety can be a motivator and prepare one to confront a crisis. When anxiety persists or occurs abnormally, it can impair functioning and lead to an anxiety disorder. In the medical setting, anxiety can be a normal coping mechanism when dealing with the stress of illness. However, if it exceeds social, psychological, or physiological needs, anxiety can become maladaptive-leading to somatic symptoms that cause distress and impairment.

Prevalence of anxiety in the medically ill

Patients with primary anxiety disorders, such as generalized anxiety disorder (GAD), panic disorder, and phobias, as well as PTSD, report a higher rate of certain medical illnesses than are observed in the general population. The National Comorbidity Survey Replication showed a 12-month prevalence rate of 3.1% for GAD and a lifetime prevalence rate of 5.7%; the lifetime prevalence for panic disorder was found to be 4.7%, with a 12-month prevalence of 5.7%.

 In comparison, the general prevalence of GAD in primary care is thought to be 8%.

 suggest that an estimated 25% of 441 chest pain complaints in an emergency department (ED) setting were due to panic attacks.

Specific medical phobias, such as fear of blood, needles, or MRIs (due to claustrophobia), are quite common. Combined blood-injectioninjury phobias have been found to have a lifetime prevalence of over 3% in a general population sample.

 The presence of these phobias is of concern because they can contribute to patients having difficulty in pursuing medical care.

The lifetime prevalence of PTSD is 6.8%, with a 12-month prevalence estimated to be 3.5% in the general population.1 In a primary care setting, 12% of patients examined were found to have PTSD

; 30% to 40% of motor vehicle accident survivors were found to have PTSD, so were 20% to 45% of burn victims.

 The diagnosis of an acute distress disorder strongly predicted the presence of PTSD 6 months later.

 Although PTSD and acute stress disorder are categorized under trauma and stressor-related disorders in DSM-5, in this article, PTSD is considered as a primary anxiety disorder.

Impact of anxiety disorders on medical illness

Anxiety disorders cause diminished functioning and well-being along with increased suffering; these effects are amplified in the presence of comorbid medical illness. As a group, they contribute to symptom severity in medical populations, functional impairment, and increased risk of disease progression. Anxiety also plays a role in increased health care use and cost, greater number of iatrogenic complications, and decreased adherence to treatment.

Beyond psychosocial implications of anxiety disorders, there are also physiological effects of anxiety. Anxiety can create excessive sympathetic activation, alteration in inflammatory response, and disruption of the hypothalamic-pituitary-adrenal axis-predisposing patients to increased health risks. Comorbid anxiety disorders and medical illnesses often lead to a self-perpetuating cycle in which a chronic medical illness negatively affects level of function, leading to depression and anxiety, which, in turn, can worsen the underlying medical condition. The dynamic interplay between comorbid anxiety disorders and medical illnesses can pose diagnostic and management challenges.

Primary anxiety disorders and comorbid physical illnesses

Patients with primary anxiety disorders are more likely to suffer from GI, respiratory, cardiac, and neurological disorders, even after adjusting for confounding factors such as sex, depression, and substance use disorders. Among patients with panic disorder, GAD, and PTSD, rates of irritable bowel syndrome are much higher than in those with no psychiatric diagnoses. Similarly, panic disorder, GAD, and phobias are strongly associated with asthma and cancer. Anxiety disorders are associated with an increased incidence of cardiovascular disease, such as myocardial infarction, angina, sudden cardiac death, and hypertension, and frequent panic attacks are associated with worse cardiac outcomes. PTSD is associated with increased risk of cardiovascular disease, increased rates of re-hospitalization, and decreased adherence to treatment regimens. Primary anxiety disorders, particularly panic disorder, are also comorbid with seizure disorder. Finally, social anxiety disorder and panic attacks are often seen in patients with Parkinson disease.

Secondary anxiety and secondary anxiety disorders

Since there is a bidirectional relationship between anxiety and medical illnesses, many severe medical conditions can lead to secondary anxiety that ranges from normal psychological reactions to illness to intense anxiety or preoccupation about somatic sensations, which result in impaired functioning. A diagnosis of a severe, chronic, or debilitating medical illness will invariably elicit a number of negative emotions, such as anxiety, fear, sadness, and anger. When the emotional reactions are out of proportion to the context and lead to significant impairment in functioning, secondary anxiety disorder (ie, adjustment disorder with anxiety) can be the result.

DSM-5 conceptualizes adjustment disorder as a stress-response syndrome that occurs after exposure to a distressing event and is listed under traumaand stressor-related disorder. Secondary anxiety can also result from the effects of substance use, either from intoxication or withdrawal from a drug or anxiety as an adverse effect of a medication. 

Anxiety secondary to general medical conditions

Some medical disorders, such as pheochromocytoma and hyperthyroidism, can produce anxiety directly by affecting neuroendocrine systems. Other medical disorders produce anxiety indirectly through autonomic arousal that the patient interprets as a psychological state, such as anxiety experienced during an acute myocardial infarct or pulmonary embolism. Medical conditions that can produce symptoms of anxiety are listed in 

Anxiety as an impersonator of medical illness

Anxiety can be camouflaged as somatic symptoms to mimic a medical illness, especially in the primary care setting. Some of the somatic expressions of anxiety include tachycardia, palpitations, sweating, flushing, dry mouth, dizziness, tremor, muscle tension, headaches, and fatigue. These symptoms could present as a “false alarm” because of an underlying anxiety disorder or a somatoform disorder. The somatic component complicates the overall picture and results in more functional impairment and higher use of medical resources.

There is a major revision of somatoform disorders in DSM-5. Psychological factors affecting medical conditions is a new diagnosis under the classification of somatic symptom and related disorders. Psychological factors include psychological distress, patterns of interpersonal interaction, coping style, and maladaptive health behaviors. In DSM-5, individuals with high health anxiety and significant somatic symptoms are given a diagnosis of somatic symptom disorder; this replaces somatization disorder in DSM-IV. Alternatively, individuals with high health anxiety without somatic symptoms may receive a diagnosis of illness anxiety disorder, which replaces hypochondriasis in DSM-IV.

The anxious patient in the medical setting can be diagnostically challenging. A key component to the clinical approach toward an anxious patient is differentiating pathological anxiety from a regular emotional response. If an anxious response is disproportional to a medical illness or illness exacerbation, etiologies for anxiety need to be investigated systematically using a biopsychosocial approach.

Biologically, acute anxiety may be the first sign of exacerbation of an underlying illness, an undiagnosed medical condition, or substance intoxication or withdrawal. To aid in diagnosis, the patient examination includes a detailed history; focused physical examination; complete review of medications; collateral information; and diagnostic testing, such as toxicology screens. For example, a patient with a history of myocardial infarction may present to the ED with panic attacks along with palpitation and numbness. The treating physician must first rule out recurrent cardiac abnormalities, pulmonary issues, new-onset neurological abnormalities, medication or substance intoxication/withdrawal, and other conditions that require immediate interventions.

Psychologically, an anxious reaction to a medical illness may be due to a patient’s uncertainty regarding a medical diagnosis or prognosis. In the medical or surgical ward, factors that contribute to anxiety include being unfamiliar with the hospital setting, staff, and procedures. From a social perspective, fears about losing functional capacity or becoming overly dependent on others may be a contributing factor; fear of death is another source of anxiety. Involvement of family and social supports can provide greater reassurance in these situations.

Managing acute anxiety pharmacologically differs significantly from managing chronic anxiety disorders (

). Benzodiazepines are effective for acute anxiety and ideally should be limited to short-term use. Lorazepam is commonly used for anxiety-induced chest pain or anxiety associated with chest pain. Patients with cancer comorbidities may benefit from benzodiazepines because they also help with nausea and insomnia. Benzodiazepines should be used with caution in patients with a history of substance abuse and in the elderly who have cognitive impairment and who may be at risk for falling. Benzodiazepines can also decrease respiratory drive in patients with obstructive sleep apnea and severe chronic obstructive pulmonary disease (COPD).

Low-dose atypical antipsychotics (such as quetiapine, risperidone, and olanzapine) are effective in acute debilitating anxiety that causes obsession, disorganized thinking, and overwhelming distress and that interferes with medical care

; however, there is no well-designed study of this class in the treatment of anxiety. Mirtazapine, an Î±2-antagonist and serotonin antagonist, has been found to work quickly and effectively for acute anxiety associated with insomnia and poor appetite.

 Orally disintegrating tablets of mirtazapine, clonazepam, olanzapine, and risperidone are available and may be helpful for patients with dysphagia or with a diet restriction. Some of the benzodiazepines and atypical antipsychotics also have oral solution and injectable forms, which are very useful in acute medical and surgical settings.

In outpatient clinics, a patient’s anxiety may arise from a perceived negative self-image in the physician’s eyes. This example may be particularly pertinent in situations in which patients either caused or exacerbated their illness (eg, tobacco use). Excessive worry in these situations may contribute to reluctance in following up with health care appointments, and to denying or failing to disclose information that ultimately leads to treatment delays or less optimal treatment. Therefore, while firm reminders are appropriate, harsh critique of the patient is unwarranted and may contribute to poorer treatment adherence.

SSRIs are the first-line agents for chronic anxiety disorders and are generally well tolerated by elderly patients.

 Sertraline, citalopram, and escitalopram have fewer drug-drug interactions than paroxetine and fluoxetine.9 Sertraline has the most evidence of safety and effectiveness in patients with significant cardiovascular disease.

SNRIs, such as duloxetine and venlafaxine, are FDA-approved for primary anxiety disorders and neuropathic pain. Buspirone, a partial serotonin-2 agonist, is recommended for chronic anxiety in the elderly and in patients with COPD, sleep apnea, or substance abuse. Buspirone is a category B drug for pregnancy and thus is not expected to harm an unborn baby; the other anxiolytic agents are classified under category C or D.

Anticonvulsants and Î²-blockers can be used for both acute and chronic anxiety. Valproic acid is used for anxious agitation seen in patients with traumatic brain injury, mental retardation, or advanced dementia. Gabapentin, a Î³-aminobutyric acid (GABA) analogue, is not only effective in patients with acute GABAergic withdrawal anxiety but is also used off-label for chronic anxiety, such as panic disorder and PTSD. Pregabalin can be considered for social phobia and GAD. Î²-Blockers reduce the sympathetic surge of anxiety, as seen in performance anxiety and social phobia

; they are also the first-line treatment for akathisia as an acute form of anxiety.

Psychotherapy is also effective for managing anxiety in the medically ill. Supportive therapy and brief cognitive-behavioral therapy can be readily used at bedside or in an office. Psychodynamic psychotherapy is an option for those patients who are more resilient and whose condition is less acute. Other therapies, such as hypnosis, meditation, and biofeedback, can play a role in both anxiety and physical symptoms.

Treatment modalities should be discussed with the patient to ensure autonomy, minimize the subjective feeling of losing control, increase adherence, and ultimately strengthen the therapeutic alliance. Collaboration with other treatment teams is essential in reducing health care utilization.

Dr Dong is Assistant Professor of Psychiatry at INOVA Fairfax Hospital in Falls Church, Va. Drs Noorani and Vyas are Psychiatry Residents in the department of psychiatry and behavioral sciences at The George Washington University, in Washington, DC. Drs Balgobin and Torres-Llenza are Psychosomatic Medicine Fellows at INOVA Fairfax Hospital and The George Washington University. Dr Crone is Associate Professor of Psychiatry at INOVA Fairfax Hospital and The George Washington University. The authors report no conflicts of interest concerning the subject matter of this article.

 Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. 

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 McKibben JB, Bresnick MG, Wiechman Askay SA, Fauerbach JA. Acute stress disorder and posttraumatic stress disorder: a prospective study of prevalence, course, and predictors in a sample with major burn injuries. 

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The authors examine anxiety in the medically ill: its presence secondary to or as an impersonator of physical illness and its diagnostic and management challenges.

Author | Catherine Crone, MD

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