Management of Immunosuppressant-Induced Psychosis Across the Lifespan

Background/Significance:

Immunosuppressants, particularly glucocorticoids and calcineurin inhibitors, have been reported to induce psychosis from early in the medication course to years later. Patients often remain on immunosuppressants chronically, making it imperative to assess for immunosuppressant-induced neurotoxicity and to consider longitudinal treatments. Presenters will review a case of a patient with psychosis on multiple immunosuppressants, discuss current literature on mechanisms of action, and review diagnostic considerations and management recommendations.

Case:

A 60-year-old female with a reported psychiatric history of schizophrenia and a medical history of renal transplant 10 years prior, presented to the hospital with worsening paranoia and auditory hallucinations in the setting of psychiatric treatment nonadherence. Upon further clarification, it was discovered that her psychotic symptoms initially started 2 years following renal transplantation. Her immunosuppressants included tacrolimus, mycophenolate mofetil, and prednisone, to which she had been adherent. Due to the timeline of her symptoms, the diagnosis was modified to substance-induced psychotic disorder secondary to immunosuppressants, rather than schizophrenia; she was stabilized on long-acting aripiprazole and discharged with outpatient follow-up.

Discussion:

Current hypotheses on the mechanisms of glucocorticoid-induced psychosis postulate hippocampal dysfunction via stress on the HPA axis, and induction of tyrosine hydroxylase (Hyunh, 2021). Calcineurin inhibitors like tacrolimus have been found to inhibit NMDA-induced neurotransmitter release, causing compensatory glutamate release and psychotic symptoms. Additionally, PPP3CC, a calcineurin-related gene, has been linked with susceptibility to schizophrenia (Brosda, 2021).

Given the variability in onset of immunosuppressant-induced psychosis, it is imperative that it is included in the differential for patients with current or prior immunosuppressant use, in addition to primary psychiatric disorders and psychosis secondary to other medications (Dubovsky, 2012). Initial management strategies include collaborating with consultants to taper or discontinue the offending agent, or switching to another agent. If maintenance immunosuppressants are required, antipsychotic selection can be based on side effect profiles and shared receptor affinities with the offending immunosuppressant (Huynh, 2021). The interdisciplinary team is a key component when promoting treatment adherence. While research on the specific use of long-acting injectable (LAI) antipsychotics in cases of immunosuppressant-induced psychosis is limited, they have proven to be useful in optimizing adherence to psychotropics and immunosuppressants by simplifying the overall medication regimen, which can be valuable in these medically complex patients (Truett, 2022).

Conclusion/Implications:

Considering the chronicity of immunosuppressive treatment, an interdisciplinary approach to the management of immunosuppressant-induced psychosis prioritizing adherence is imperative, with special considerations for LAI antipsychotics. Further research topics include longitudinal studies of the efficacy of LAIs in management of immunosuppressant-induced psychosis, as well as specific psychiatric risks associated with individual immunosuppressants.

References:

Brosda J, et al. Treatment with the calcineurin inhibitor and immunosuppressant cyclosporine A impairs sensorimotor gating in Dark Agouti rats. Psychopharmacology. 2021;238(4):1047-1057.

Dubovsky AN, et al. The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. Psychosomatics. 2012;53(2):103-115.

Huynh G, et al. Pharmacological Management of Steroid-Induced Psychosis: A Review of Patient Cases. J Pharm Technol. 2021;37(2):120-126.

Truett C et al. Psychotic Disorders and Organ Transplantation. In Transplant Psychiatry. 2022: 33-38.