Lung transplant recipients are maintained on lifelong immunosuppressive regimen and prophylaxis against opportunistic infections. They certainly experience adverse effects from these medications that tend to contribute to poor perceived quality of life. This in turn can contribute to depression and anxiety [22]. The effect of high dose glucocorticoids (an essential component, early in the course of lung transplantation) on mood and coping skills, with increase in depression and anxiety cannot be understated [25–27]. In addition to this, Tacrolimus and Cyclosporine (calcineurin inhibitors, the core component of immunosuppressive regimen after lung transplantation) can cause insomnia, restlessness and tremor [28–31]. Combined, these adverse effects can certainly interfere with coping skills and impact the quality of life. Additionally, difficulties encountered while navigating loss of control and dependence on caregivers (for activities of daily living), family and friends can potentially lead to significant distress and overall mood changes.

It is imperative that lung transplant recipients receive life-long immunosuppression to prevent lung allograft rejection. It does add a significant burden to the recipient and could potentially lead to non-adherence. There are published data in kidney, heart and liver transplant recipients that medical non-adherence is the single most important risk factor for acute allograft rejection and graft loss. In heart and kidney transplant recipients, pre-transplant adherence was identified as a significant predictor of survival after transplantation [32–40]. Moreover, in heart transplant recipients, non-adherence to medical regimen during the first year after transplantation increased the risk of acute cardiac allograft rejection by over fourfold [37]. This finding highlights the importance of urging all solid organ transplant recipients to remain adherent to the prescribed medication regimen. It was reported that adherence to medical regimen worsens over time after heart transplantation [41]. A plethora of psychosocial factors, stressors and physical complications have been empirically cited as potential factors that can contribute to poor quality of life that in turn can lead to depression, anxiety and poor adherence to medical regimen and clinical monitoring in lung transplant recipients (Table 7.1 [42–48]). In addition to some of the above identified factors, other reported risk factors for non-adherence include lower age particularly adolescents, male gender, higher educational level, longer period after lung transplantation and depression. Bosma et al. reported 7.7% rate of non-adherence to immunosuppressive therapy in recipients, one year after lung transplantation. They note that recipients less than 1 year after lung transplantation were not included due to logistic limitations. In their study they noted that age, especially adolescents and adults with decreased ability to care for self appeared to be more at risk of non-adherence [49].

Following lung transplantation, recipients often experience depression and anxiety and associated perceived poor health-related quality of life. There is a high risk that this ultimately could lead to non-adherence to medical regimen and clinical monitoring with a risk of acute lung allograft rejection and adverse short-term and long-term outcomes. In addition, lung transplant recipients are already on numerous medications making addition of medications to treat depression and anxiety more difficult. It comes at an added risk of serious drug to drug interactions as well (Table 7.2 [50, 51]).

A number of strategies to treat depression and anxiety after lung transplantation were utilized. Broadly, they can be divided into non-pharmacologic and pharmacologic interventions. Non-pharmacologic strategies include cognitive psychotherapy, family or group therapies and complimentary therapies such as relaxation techniques, mind–body therapies, prayer and support groups [20, 52]. They could potentially help with the coping process and a perception of better quality of life. Pharmacologic therapy broadly includes antidepressant and anxiolytic medications.

Tricyclic antidepressants (TCAs) have a plethora of adverse effects and drug to drug interactions, making them a less appealing choice to use in lung transplant recipients. Selective serotonin reuptake inhibitors (SSRIs) and new-generation antidepressants such as mirtazapine are the first-line medications of choice to treat symptoms of depression. Their favorable adverse effect profile with fewer drug to drug interactions particularly with immunosuppressive medications make them a very appealing first line of choice (Table 7.1). Unfortunately they do cause inhibition of hepatic CYP450 enzyme system. Caution should be exercised when SSRIs are initiated. They increase the levels of immunosuppressive medications particularly the calcineurin inhibitors (CNIs), namely cyclosporine and tacrolimus, more so with the former. Hence, it is highly recommended that CNI drug levels are periodically monitored and necessary adjustment to the dosage made to maintain optimum levels and avoid potentially life-threatening adverse effects and toxicities. Caution should be exercised with careful consideration toward other drug-to-drug interactions. An important example is prolongation of Q-T interval which needs to be closely monitored with frequent ECG testing.

Anxiety and insomnia can be crippling in individuals with end-stage lung disease and in lung transplant recipients. Although benzodiazepines are commonly used for these symptoms, they can cause respiratory depression and blunt the arousal response to hypercapnia even at therapeutic doses in a few individuals [4, 53]. Mirtazapine is promising and has a dual mode of action without the adverse effects of benzodiazepines and seems beneficial for depression and anxiety [54].

Individuals with end-stage lung disease and lung transplant recipients are a heterogeneous group. These conditions impose significant psychosomatic limitation by way of depression and anxiety. Evidence clearly indicates that depression and anxiety are the most common psychological sequelae of end-stage lung disease and complications after lung transplantation. Despite such limitations, when successful, lung transplantation results in survival benefit as well as quality of life benefit. It also yields in significant improvements in physical and psychological health. Clinical screening tools are an essential integral part of pre-lung transplant psychosocial assessment to assist in early identification of stressors and risk factors in individuals with potential for poor coping skills and medical non-adherence as they have a negative impact on post-lung transplant quality of life and outcomes. Heightened vigilance for symptoms and signs of depression and anxiety disorders in all individuals with end-stage lung disease and lung transplant recipients is warranted. Successful lung transplant centers have dedicated medical social workers, psychologists and psychiatrists as essential, integral members of a multidisciplinary lung transplant team. Such system would assist in screening, identification and intervention for depression, anxiety and high-risk behavior that have a negative impact on the quality of life and clinical outcomes after lung transplantation. There is a definite role for psychological (non-pharmacological and pharmacological) interventions in individuals with end-stage lung disease and after lung transplantation, at the earliest possible window, to alleviate symptoms related to depression and anxiety and to assist with coping and improve overall quality of life and outcomes after lung transplantation.