Treatment of anxiety and depression in transplant patients - Pharmacokinetic considerations

Depressive and anxiety disorders appear during the transplant process due to psychological stressors, medications and physiological disturbances. Treatment is necessary to prevent impact on patient compliance, morbidity and mortality. Psychotropic medications provide an effective option, although most are only available as oral formulations. Because of this, they are more susceptible to alterations in pharmacokinetic behaviour arising from organ dysfunction in the pretransplant period. Kinetics are also an issue when considering potential drug-drug interactions before and after transplantation. Prior to transplant, organ dysfunction can change the pharmacokinetic behaviour of some psychotropic agents, requiring adjustment of dosage and schedules. Thoracic or abdominal organ failure may reduce drug absorption through disturbances in intestinal motility, perfusion and function. Cirrhotic patients experience increased drug bioavailability due to portosysternic shunting, and thus dosage is adjusted downward. In contrast, dosage needs to be raised when peripheral oedema expands the drug distribution volume for hydrophilic and protein-bound agents. Drug clearance for most psychotropic medications is dependent upon hepatic metabolism, which is often disrupted by endstage organ disease. Selection of drugs or their dosage may need to be adjusted to lower the risk of drug accumulation. Further adjustments in dosage may be called for when renal failure accompanies thoracic or abdominal organ failure, resulting in further impairment of clearance. Studies regarding the treatment of anxiety and depressive disorders in the medically ill are limited in number, but recommendations are possible by review of clinical and pharmacokinetic data. Selective serotonin reuptake inhibitors are well tolerated and efficacious for depression, panic disorder and post-traumatic stress disorder. Adjustments in dosage are required when renal or hepatic impairment is present. Among them, citalopram and escitalopram appear to have the least risk of drug-drug interactions. Paroxetine has demonstrated evidence supporting its use with generalised anxiety disorder. Venlafaxine is an alternative option, beneficial in depression, post-traumatic stress and generalised anxiety disorders. Nefazodone may also be considered, but there is some risk of hepatotoxicity and interactions with immunosuppressant drugs. Mirtazapine still needs to be studied further in anxiety disorders, but can be helpful for depression accompanied by anorexia and insomnia. Bupropion is effective in the treatment of depression, but data are sparse about its use in anxiety disorders. Psychostimulants are a unique approach if rapid onset of antidepressant action is desired. Acute or short-term anxiolysis is obtained with benzodiazepines, and selection of particular agents entails consideration of distribution rate, half-life and metabolic route.