(PO-167) (PO-167) Serotonin syndrome morphing into acute dystonia due to polypharmacy: A deep dive into the world of pharmacokinetics and pharmacodynamics

Has Audio

Background: Polypharmacy has become commonplace in the care of psychiatric patients especially when they suffer from other medical issues requiring medication (Kingsbury, 2007). Unexpected medication interactions lead to unanticipated complications. Here, we present a case not previously described in the literature that highlights cascading pharmacokinetic and pharmacodynamic interactions between duloxetine, nortriptyline and metoclopramide, which led to serotonin syndrome followed by an acute dystonic reaction.

Case: Ms. M is a 42-year-old female with complex past medical history including asthma (on home oxygen), T2DM, OSA on CPAP, HTN, HLD, CKD (baseline Cr 1.6) and MDD admitted to the hospital after a fall. Home medications included duloxetine 60 mg BID, metoclopramide 10 mg QID PRN, and nortriptyline 150 mg QHS. She had an AKI due to intractable nausea and vomiting, and her metoclopramide was converted to 10 mg IV QID scheduled. Psychiatry was consulted on hospital day 5 due to bizarre behavior and hallucinations. On exam, she was found to have clonus in her extremities, and was acutely confused, actively hallucinating, and tremulous. She complained of chills, diarrhea, and significant akathisia and was diagnosed with serotonin syndrome. Duloxetine and nortriptyline were decreased with a plan to taper entirely. The next day, patient developed periods of sustained upward gaze concerning for oculogyric crisis and muffled speech with clonus no longer appreciable on exam. IM benztropine was given due to concern for vocal cord involvement and provided rapid symptom relief. She was ultimately discharged after cessation of the three offending medications without recurrence of serotonin syndrome or dystonia.

Discussion: The following factors contributed to her initial serotonin overload on a previously tolerated outpatient medication regimen: increased levels of metoclopramide after her AKI, scheduling this medication and conversion to IV formulation (Bateman 1981); increased nortriptyline levels due to CYP2D6 inhibition (from increased metoclopramide dosing); and increased duloxetine levels from CYP2D6 inhibition and her AKI (duloxetine package insert; Dawlilng 1981). Undisclosed noncompliance with the outpatient medication regimen is another potential cause. Tapering nortriptyline resolved the serotonin syndrome but likely unmasked the subsequent dystonic reaction to metoclopramide, given its anticholinergic properties.

Conclusion: Our case highlights numerous pharmacokinetic and pharmacodynamic interactions relevant for C-L psychiatrists. Patients on complex and untested regimens have the potential for numerous unexpected medication interactions.

References:

Bateman DN, Gokal R, Dodd TR, Blain PG. The pharmacokinetics of single doses of metoclopramide in renal failure. Eur J Clin Pharmacol. 1981;19(6):437-441. ta

Cymbalta (duloxetine hydrochloride) capsules. Package insert. Eli Lilly and Company, 2010

Dawlilng S, Lynn K, Rosser R, Braithwaite R. The pharmacokinetics of nortriptyline in patients with chronic renal failure. Br J Clin Pharmacol. 1981;12(1):39-45.

Kingsbury SJ, Lotito ML. Psychiatric Polypharmacy: The Good, the Bad, and the Ugly. Psychiatric Times. 2007;24(4). doi:https://www.psychiatrictimes.com/view/psychiatric-polypharmacy-good-bad-and-ugly

Learning Objectives:

Go through a case of polypharmacy and review pharmacokinetic and pharmacodynamic interactions causing multiple psychiatric emergencies in a single admission.

Presenting Author(s)

Margaret Cinderella, MD
– C-L Fellow, UNC Hospital System, Winston Salem, North Carolina, United States

Co-Author(s)

Nona A. Nichols, MD
– Consultation-Liaison Psychiatry Fellow, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
Sahil Munjal, MD
– Assistant Professor, Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States