Case Presentation: A 48 year-old woman presented with altered mental status and combativeness. She had been her usual self earlier in the day, but had been complaining of a headache and fatigue since the prior day. She woke up from a nap confused and agitated prompting her husband to call emergency personnel. Medical history included liver failure from Budd Chiari syndrome requiring transplant and the transplanted liver was now cirrhotic. She had been admitted for hepatic encephalopathy several times in the past year. Her history also included poorly controlled depression.
Lab work was not suggestive of infection or electrolyte abnormality to explain her altered state and head CT revealed no acute process. Since no alternative diagnosis was apparent, initial treatment was directed by a presumptive diagnosis of hepatic encephalopathy. However, her symptoms did not improve with adequate dosing of lactulose and rifaximin. Tachycardia, hypertension, agitation, ocular clonus, deep tendon hyperreflexia, spontaneous muscle clonus, muscle rigidity, flushed skin and diaphoresis were present on exam the following day.
Chart review revealed she had recently been switched from citalopram to duloxetine by her primary care provider for poorly controlled depression. Of note, citalopram had been appropriately dosed for hepatic impairment but there is no recommended safe dose of duloxetine for patients with liver impairment.
Supportive care for serotonin syndrome was then initiated. Her mental status improved over the following forty-eight hours. Her hospital course was complicated by acute kidney injury and fluid overload requiring diuretics with subsequent allergic reaction to a diuretic agent. Duloxetine had been held at time of admission and was permanently discontinued at discharge. She is currently receiving no pharmacological treatment for depression.
Discussion: Liver disease is a risk factor for depression and correlates with the severity of liver impairment. Depression affects quality of life and has a negative impact on disease course. Patients who are depressed are less likely to survive to transplant. Unfortunately, general practitioners are less likely to initiate anti-depressants in patients with complex medical states such as chronic liver disease. This hesitancy may be due to a lack of research to support or refute the efficacy and safety of anti-depressants in this population.
Further guidance is needed, in the form of clinical research and society recommendations, especially for patient scenarios with first-line treatment failure. This is to eliminate this population’s barrier to receiving safe and effective care for depression.
Conclusions: Guidelines are needed for the pharmacological treatment of depression in liver impairment. While there are dosing recommendations for some therapies, general practitioners lack further guidance and it leads to adverse patient events.