Understanding the Breadth and Depth of C-L Psychiatry: Complex Psychopharmacology in Medically Ill Patients

Consultation-liaison (C-L) psychiatrists work at the interface between psychiatry and medicine and must often treat medically compromised patients for psychiatric illness. The following case describes the role of C-L psychiatrists in identifying the risks and benefits of initiating a psychiatric medication that could result in QTc-prolongation in a medically frail patient receiving hemodialysis.

Case Study

Mr. T is a single man in his 70s with hypertension, coronary artery disease, and end-stage renal disease requiring hemodialysis. He has a psychiatric history of major depressive disorder and made a suicide attempt three years ago. After missing several hemodialysis sessions, he presented to the emergency department and was admitted with failure to thrive, significant weight loss, and electrolyte disturbance. He was withdrawn, irritable, subtly confused at times, and reluctant to pursue hemodialysis; he also passed up hospital meals. The nutrition team recommended artificial nutrition. The patient’s team consulted with the C-L psychiatry service to further evaluate the cause of his poor oral intake and to optimize depression management.

Mr. T described progressive worsening of depressive symptoms, most notably low mood, anhedonia, loss of appetite, insomnia, loss of energy, and slowed thoughts and physical movement. Symptoms were typically most severe on the afternoon following a hemodialysis session, with some abatement the next day. His current medications included fluoxetine and mirtazapine for depression and hydroxyzine for pruritus associated with chronic kidney disease, which Mr. T described as maximally distressing.

The C-L psychiatry team considered starting him on an atypical antipsychotic—low-dose olanzapine—to augment treatment of depression, noting the possibility of mild delirium and the benefits of olanzapine to stabilize his sleep-wake cycle. The receptor profile of olanzapine allowed the team to make the best use of anticipated side effects including appetite stimulation, weight gain, antiemetic effects, nighttime sedation, and antihistaminergic activity for pruritus.

To carefully weigh the benefits and risks of initiating olanzapine, as with any antipsychotic in a medically complex patient, the C-L team reviewed the patient’s ECG, which showed normal sinus rhythm, heart rate of 60 bpm, and a corrected QT interval (QTc) of 500 ms. Further chart review revealed a history of prolonged QTc between 500 ms and 530 ms over the past several years. After careful consideration of the risks and benefits of adding an antipsychotic, the C-L team initiated low-dose olanzapine, as the benefits to quality of life and alignment with the patient’s goals outweighed the rare risk of Torsades de Pointes (TdP).

What is the risk of TdP in a patient on hemodialysis?

TdP is a rare form of polymorphic ventricular tachycardia and may lead to sudden cardiac death, which is the leading cause of death of hemodialysis patients. Prolongation of the QT interval is most commonly the result of sluggish and erratic ventricular repolarization, which may lead to TdP. As such, the QT continues to be the most widely utilized tool for assessing risk for TdP and is a major drug-safety benchmark used by the Food and Drug Administration.

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Strikingly, patients with end-stage renal disease are particularly susceptible to acquired long-QT syndrome for various reasons, including high prevalence of comorbid cardiac disease, large fluid and electrolyte shifts during hemodialysis, and tendency to receive numerous medications (polypharmacy). Of particular concern are rapid shifts of serum potassium and calcium, each with key roles in cardiac membrane stability, contractility, and repolarization. These fluctuations of electrolytes and fluid may have been even more profound for Mr. T, who had difficulty engaging in regularly scheduled hemodialysis sessions.

In patients receiving hemodialysis, mood as well as medical status may fluctuate throughout the week depending on the day of dialysis. Physical fatigue, discomfort, and hopelessness because of the continued reliance on a machine to sustain life may all contribute. Additional considerations include the risk of delirium in the peri-dialysis period, to which Mr. T was vulnerable.

What is the role of the C-L psychiatrist?

C-L psychiatrists use their knowledge and experience to identify and weigh complex medication-associated cardiac risks in medically ill patients. In this case, the potential benefits of improving quality of life through improved mood, appetite, nausea, weight, sleep, and pruritus were weighed against the risk of a rare but potentially life-threatening arrhythmia in a patient with QTc prolongation risk factors.

The availability of C-L psychiatrists in general hospitals to consult on high-risk patients and make rounds with high-risk services can result in reducing morbidity, mortality, and health care costs and higher rates of patient and provider satisfaction. ■