Organ transplant & the psychiatrist: An overview

Introduction

Organ transplant/transplantation (OT) has been defined as the therapeutic grafting of an organ from a living or dead body to a living body1. OT is a complex, invasive and major surgical procedure which carries tremendous expectations from the OT candidates and caregivers for saving life and improving the quality of life (QOL). Thus, starting from the onset of the end stage organ disease (ESOD), undergoing evaluation for candidacy, surgical procedure and related complications, and ending with death, all through these phases OT and organ donation are inherently enormously distressing. Also, OT is bound to ethical and legal issues. In the developing countries, the picture gets complicated by the psychosocial milieu being different in terms of poverty, underdeveloped protective medical institutional mechanisms, family structure and functioning, cultural norms and values related to organ donating/receiving. Emerging evidence shows that pre-operative psychosocial variables can predict post-transplant psychiatric adjustment for most organ types2, and meta-analyses have shown that post-transplant QOL improves for social, physical and daily activity functioning, but not consistently for psychological health34. This implies that while medico-surgical teams take better care of the physical health, they may leave out the psychological perspective. The medico-surgical teams may overlook psychological distress, especially if underplayed by the subjects.

This overview highlights the psychiatrist's perspective on psychosocial and medication issues related to the organ recipients, donors, and caregivers, and their effect on the OT outcome. The aim is to highlight the role of the psychiatrist and to sensitize the medical fraternity in general and the OT teams in particular. The literature search strategies included electronic databases and manual searches of relevant publications or cross-references. Electronic search included PubMed and other search engines (Embase, Science Direct, Google Scholar) for the years 2005-2014. Cross-searches often yielded additional relevant material. The search terms used in various combinations were: transplantation, psychiatrist, psychiatry, living donors, caregivers, psychotropics. The relevant articles were selected based on their importance for psychosocial and psychiatric aspects of OT. Accordingly, we selectively focussed on good and large scale relevant reviews and meta-analyses. Thus, this review attempts to give an overview of the area and is not a systematic review of the area5. Relevant Indian research is summarised separately.

Organ transplant: A heavy burden

Organ transplant is a continuum of different phases, each associated with its own individual, social and economic problems.

1. End stage organ disease (ESOD) is the patient's worst clinical state with failed organ function. As a matter of life and death, it marks the beginning of OT.

2. OT evaluation involves various steps to achieve OT candidacy, at the cost of a performance anxiety and the fear of omission.

3. Waiting for organ donation is the most distressing phase. Continued deterioration of health and critical medical care like dialysis is associated with10-18 per cent patients dying, and 5 per cent becoming medically unsuitable; another 2 per cent refuse OT6. The greatest obstacle is the shortage of donated organs; in the USA 40 per cent candidates wait for >2 years before they get an organ6.

4. Transplantation and after, means dealing with a complex OT procedure, perioperative complications, and a post-OT life with constant threat to survival, and inevitable and often distressing dependence on caregivers for help on various counts.

Unique dual role of psychiatrist in transplantation

Comprehensive pre-transplant psychosocial evaluation helps to get a more complete understanding of mutual, and sometimes contradictory, expectations and needs of transplant candidates, donors, caretakers and the transplant team. The psychiatrist plays a unique dual role in serving both the needs of the transplant team as well as the transplant patient, donor and the carers7. The psychiatrist also has a major role in identifying problematic areas/issues both pre- and post-transplant and address those to seek improved outcomes.

Pre-transplant psychosocial evaluation

It is a stepping stone for OT candidacy. Limited availability of donor organs, need for psychological sophistication, good family support, considerable medical and financial resources for better care and outcome - all dictate the selection of only those candidates who have the best chance of post-OT outcome. To select the best candidate for transplantation, there is a need to screen the patient's coping skills for stressors, co-morbid psychiatric conditions and their pre- and post-transplant monitoring and treatment, capacity to understand the transplant process and to provide informed consent, ability to collaborate with the transplant team and to adhere to treatment, substance use/abuse history, recovery, and ability to maintain long-term abstinence, health behaviours that may influence post-transplant morbidity and mortality like eating or exercise habits, level of social support available to the candidate for pre- and post-transplant phases and psychosocial needs of the patient and family and plan for services during the waiting, recovery, and rehabilitation phases of the transplant process8.

Some of the important aspects of organ transplant will be considered in the following sections which demand a psychiatrist's expertise:

Treatment adherence

Treatment adherence generally includes regular intake of medications, monitoring vitals, undergoing diagnostic tests, following dietary and exercise protocols, abstinence from substance abuse, and regular follow up. A meta-analysis of 147 studies across all organ types showed average non-adherence per 100 PPY (persons per year) to be 1-4 for substance use, 19-25 for immunosuppressants, diet, exercise, and other requirements9.

A review of 17 studies showed non-adherence to be associated with poor clinical outcome, contributing to 20 per cent of late acute rejection episodes, lower number of quality adjusted life years and lower lifetime costs because of shorter survival10. Thus, it is very essential to identify candidates with ambivalence about treatment and prior history of non-adherence, substance abuse, poor social support, and poor organisational skills as they are more prone for treatment non-adherence.

Risky health behaviours

These include substance abuse, poor eating habits and sedentary lifestyle leading to obesity. Studies have shown that pre-transplantation BMI >30 kg/m² or body weight >140 per cent of ideal, decrease survival rate among transplant recipients compared to controls among renal11 and heart12 cases, respectively. Another study showed that compared to controls nutritional counselling of OT subjects, once weekly for a month and once monthly for next three months, reduced post-transplant weight gain13. Presumably poor outcome may be reduced by identifying reasons and risk factors for non-adherence and risky health behaviours, educating patient and family members regarding the same, making plan for monitoring both pre- and post-OT, and written informed behavioural and contingency contracting making the patient responsible for own acts. Recently, efforts have been made to develop a programme based on prevailing evidence to promote self-management skills for behaviours such as undesired weight gain, exercising and smoking14.

Psychiatric disorders among OT cases

Like other chronically medically ill subjects, OT cases are also at higher risk for psychiatric disorders. It may be due to either the exacerbation of a pre-existing disorder or the development of new-onset disorder. With no large-scale prevalence rate comparisons yet available, no strong evidence exists that in OT the rates of psychiatric disorders vary by the organ.

Management of psychiatric disorders

The risk for psychiatric disorders rises during organ transplantation and it adversely affects the OT outcome, compliance, morbidity, and mortality. Patients with mental health disorders, when adequately controlled and socially supported, have outcomes similar to the general transplant population45. Hence, there is need for early recognition and management.

Psychotropics

Organ dysfunction during pre-transplant period changes the pharmacokinetics of psychotropic agents, requiring proper selection of the drug and the dose. Similarly in post-OT period, psychotropics selection is influenced by drug pharmacokinetics, adverse effects, and tolerability and drug-drug interactions. Studies on the treatment of psychiatric disorders in OT cases being limited, the decisions need to be based on a review of clinical and pharmacokinetic data46474849.

Psychotherapy

Empirical data regarding psychotherapeutic interventions among OT recipients are very limited. Procedures that are commonly employed in clinical settings are group therapy, educational groups, support groups, internet based regimen and mentorship programme50. A study has shown both individual and group psychotherapy to be beneficial and individual therapy to be better than group therapy. Both decrease the negative affect, increase happiness and QOL51. Another study showed telephone-based emotional support and cognitive behaviour therapy to increase QOL and social network52. Internet based intervention improved compliance, QOL, follow up care and decreased anxiety, depressive symptoms in both patients and caregivers among heart transplant recipients53. Mentorship by an already transplanted recipient augmented patient care by providing information and support from a peer perspective54.

Drug-drug interactions between immuno suppressants and psychotropics

Commonly used immunosuppressants like steroids, tacrolimus, cyclosporine and mycophenolate have narrow therapeutic index and are mainly metabolized by cytochrome P450 3A4. Specific cytochrome P450 3A4 inhibitors in decreasing order are: fluvoxamine, nefazodone>fluoxetine>sertraline , TCAs, paroxetine >venlafaxine55. There are many case reports of tacrolimus and cyclosporine toxicity, when fluvoxamine and nefazodone were added to treat depression55. In contrast, many case reports favour safe use of other antidepressants in combination with immunosuppressants. Cyclosporine increases lithium resorption by proximal tubule, so it is mandatory to monitor lithium level in patients on cyclosporine. Disulfiram may interact with the alcohol vehicle of cyclosporine and its active metabolite is an inhibitor of CYP450 3A455.

Burden among caregivers

Dependency of transplant recipients on caregivers for everything including self-care, treatment adherence, finance, transportation, and emotional support, put them under stress. Heavy burden on caregivers and negative coping styles are shown to be associated with higher levels of depression56. In a study on caregivers of lung OT cases stress related depressive and anxiety symptoms have been reported in 82 per cent caregivers. Acute illness stage was rated more stressful than rehabilitation stage. Compared to spouses, mothers were particularly vulnerable as support persons57. Another study on heart transplantation group showed employment status and caregivers’ physical health as strong predictors of post-OT distress. Increased distress was noted in early post-OT but not in later months58. In a study on renal OT group, all caregivers perceived burden, more if the patient was a male59. There was no relationship between caregiver burden score and patients’ marital status, education level, operation time, age, donor type (cadaveric or living)59. The data regarding intervention studies are lacking; the available data show group therapy, support group and web based interventions as useful strategies in alleviating distress among caregivers.

Issues of living donor

In view of the organ shortage living organ donation is an alternative to deceased organ donation. In the USA, related and unrelated living donors constitute 44 per cent of all organ donors. Of these, 95 per cent are kidney donors, four per cent are liver donors, and the remaining one per cent are pancreas, intestine and lung donors6. Donors with altruistic motivation, no ambivalence, good understanding about risks and benefits of donation, no history of psychiatric illness or substance abuse, good family support and financial stability are known to have better outcome. In a systematic review of 51 studies, 5139 living kidney donors assessed after four years showed that the majority experienced no depression (77-95%) or anxiety (86-94%), reported unchanged or improved relationship with the recipient (86-100%), and reported psychological benefits from donation in terms of gratification of helping the needy and experiencing increase self-esteem. Though most scored high on QOL measures, a small proportion had adverse psychosocial outcomes60. Another study reported a reasonable QOL among lobar lung donors, despite a subjective decline in exercise tolerance61. In a six month follow up study of 392 liver donors, 16 (4.1%) had one or multiple psychiatric complications [12 depression, 2 anxiety, 2 substance abuse, and bi-polar affective disorder (BPAD), 1 accidental overdose, insomnia, crying episodes, and worsening of obsessive compulsive disorder (OCD) each]62. It was not clearly known if the donors were inherently more prone to psychiatric problems and had concealed this during evaluation or hepatectomy; or the psychiatric problems were a consequence of hepatectomy which is a more invasive procedure with more post-operative medical complications62.

Indian scenario

There is very limited research from India on psychiatric issues related to OT. An early study reported negative emotions among kidney recipients and donors. Among the recipients the common emotions included anxiety-depression and resentment during dialysis and perioperative period, and anxiety, dependency-frustration, body image change and decreased libido on a long term basis63. Among the donors, hostility towards family members, ambivalence towards recipients, adjustment problem at work and with spouse, anxiety about surgical procedures were recorded pre- and during OT period and excessive worry about physical symptoms of recipients, depression and hypochondriacal symptoms post-OT64. A study with live kidney donors showed their morbidity, mortality and QOL remained unchanged65. Cognitive profile and depression were studied in 30 renal transplant patients which showed depression rate of 87 and 57 per cent one month before and three month after transplantation and mean IQ increased from 88.5 to 101 following transplantation especially with respect to concentration and visual organization66. In a six month to six year follow up of 50 male kidney recipients psychiatric illness was noted in 46 per cent of patients and it was more common among unmarried, high education group and high socio-economic status67.

Conclusion

Transplantation is a challenging process for patients, caregivers, and medical professionals. It is associated with substantial emotional distress with tremendous lifestyle changes and psychological stresses. Psychosocial evaluation, considered to be a gate pass for transplantation, carries great significance. Depression and anxiety are the most common psychiatric disorders among the OT candidates and recipients. Currently, there is no general consensus on how to select/reject cases for transplantation with affective disorders, psychotic disorders, personality disorders and substance dependence. As the psychiatric disorders predict poor outcome both pre- and post-OT, it calls for an aggressive management. Immunosuppressants related neuropsychiatric side effects and drug-drug interactions with psychotropics should be kept in mind while treating psychiatric disorders. Caregivers also carry significant distress and need support. A psychiatrist as a member of the OT team can be of help for better outcome of OT.