Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor approved for the treatment of heart failure with reduced ejection fraction (HFrEF). Valsartan is well studied, but sacubitril has much left to understand. This report describes a 31-year-old African American female diagnosed with HFrEF who presented with a 7-day history of psychiatric symptoms following a dose increase in sacubitril/valsartan. Prior to the dose increase, the patient had no history of psychiatric diagnoses, but upon hospital presentation, family described instances of confabulation, paranoia, delusions, hallucinations, and sleep disturbances. Laboratory tests were unremarkable, ruling out infectious processes and illicit substance use. However, cranial computed tomography scans depicted intracranial volume loss abnormal for age with commensurate mild ventricular enlargement. Sacubitril/valsartan was discontinued inpatient, symptoms resolved, and the medication intolerance was documented. Clinical trials involving sacubitril/valsartan lack systematic documentation of cognitive symptoms, but active studies exploring the role of neprilysin inhibition may expand knowledge of possible psychiatric adverse effects.
Keywords: cognition; dementia; heart failure; neprilysin inhibitor; sacubitril/valsartan.