Psychiatric issues
All transplant patients require lifelong immunosuppression. Although this should be excellent motivation for compliance, noncompliance rats across all organ types ranges from 20-50%.
Cyclosporine
Cyclosporine is derived from a fungus and is used as a primary immunosuppressive agent.
During the transplantation operation, a patient is often loaded with cyclosporine (Gengraf), which can sometimes result in delirium. Even past this, cyclosporine neurotoxicity can begin with lethargy and confusion, which sometimes requires re-intubation. ★Neurotoxicity from cyclosporine is is potentiated by hypercholesterolemia, hypertension, and hypomagnesemia. Cyclosporine neurotoxicity can progress to seizures, cortical blindness, aphasia, headache, and agitation. The incidence of neurotoxic side effects of cyclosporine has been estimated to be in the range of 25-33%. IV administration and higher doses seem to increase the incidence of neurotoxic side effects, although cyclosporine levels do not correlate with neurotoxic side effects.
Tacrolimus
Tacrolimus (Prograf) can be used as a primary immunosuppressant, as rescue therapy for those who fail cyclosporine, or as a treatment of graft-vs.-host disease. Tacrolimus causes tremor, restlessness, and akathisia, but can also be associated with cognitive impairment, agitation, and delirium. The neuropsychiatric side effects of tacrolimus are largely similar to those of cyclosporine.
Corticosteroids
Although chronic steroid use after transplantation is less common, steriods are used in high doses immediately after transplantation. Corticosteroids have been associated with psychosis, delirium, depression, and irritability.
Pharmacological issues
★It is important to be aware of medication interactions, especially through the P450 system. Consequently, carbamazepine is just bad news in this population of patients given its induction of hepatic enzymes, which decreases cyclosporine levels through 3A4. St. John's wort also induces 3A4. Fluvoxamine is a potent 3A4 inhibitor and thus can elevate cyclosporine levels. There are case reports of serotonin syndrome resulting from a combination of sertraline and cyclosporine.