Emergent Antidepressant Discontinuation Syndrome Misdiagnosed as Delirium in the ICU

Case report

Case Presentation

A 72-year-old female presented with a large hiatal hernia (>50% of the stomach was in the chest). Her past medical history was significant for COPD/asthma, obstructive sleep apnea, coronary artery disease (S/P coronary artery bypass surgery), hypertension, hypothyroidism, and gastroesophageal reflux disease. She was on duloxetine 60 mg (0.6 mg/kg) BID for depression for the past two years as an outpatient.

She underwent laparoscopic hiatal hernia repair. On postoperative day (POD) 1, she was returned to surgery due to recurrence of the hernia and development of pneumomediastinum. The patient had an endotracheal tube for positive pressure mechanical ventilation removed on POD 2, reinserted on POD 5, removed on POD 6, and reinserted on POD 12.

Oral duloxetine was given on POD 0 and 1, 8, 9, 10, 11, and 12; however, due to frequent emesis due to gastroparesis, and it is unclear how much of the drug was absorbed. She was admitted to the ICU on POD 12 due to an emesis resulting in aspiration, which caused respiratory failure.

On POD 13-25, she presented positive for delirium in the ICU (via the Consistent identification of delirium requires the use of a reliable screening tool, such as the Confusion Assessment Method for the ICU [CAM-ICU]). She required sedation with various combinations of dexmedetomidine, fentanyl, and midazolam due to agitation. Her appearance was described by the respiratory therapists as “frantic” or “panicked” when they attempted to determine the rapid shallow breathing index.

There was concern of antidepressant discontinuation syndrome, so on POD 20, the contents of the duloxetine capsule were crushed for administration, but the duloxetine pellets would not pass through the nasogastric (NG) tube. Instead, venlafaxine (another SNRI) 75 mg immediate-release tablets were cruhsed and given via her NG tube three times daily. 

As the daily dose of venlafaxine was increased, the required doses of the sedating drugs were reduced. By POD 25 these agents were completely discontinued, and the patient was liberated from mechanical ventilation.

By POD 28, she was CAM-ICU negative for delirium and no agitation or confusion was reported. She remained on venlafaxine for the remainder of her stay.

Study Author Conclusions

In Vitro Stability, Potency, and Dissolution of Duloxetine Enteric-Coated Pellets After Exposure to Applesauce, Apple Juice, and Chocolate Pudding

Design

In vitro study

Objective

To determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties

Study Groups

Duloxetine sample not exposed to food

Duloxetine Sample Exposed to Mott's Applesauce, 2 hour

Duloxetine Sample Exposed to Mott's Apple Juice, 2 hour

Duloxetine Sample Exposed to Kraft Handi-Snacks Chocolate Pudding, 30 minutes

Methods

Contents of duloxetine 20 mg capsules (pellets) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities. For dissolution, 6 replicates were tested. To acssess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food.

The dissolution testing involves assessing the drug under conditions that are similar, but not equivalent, to those in the stomach. After the set exposure time (30 minutes for the pudding, 2 hours each for the applesauce and apple juice), the pellets were rinsed from the test food by submerging the food and pellets in 0.1 N HCl. Because the chocolate pudding has a more neutral pH (-5.5-6.0), closer to that at which the enteric coating is designed to dissolve (-5.5), the duloxetine pellets were exposed to the pudding for less time (30 minutes instead of 2 hours) to reflect a practical amount of time for preparation and administration in a clinical setting.

Apple juice was intended to be used as a wash for a nasogastric tube.

Results of potency testing of duloxetine enteric-coated pellets

No food

Apple sauce

Apple juice

Chocolate pudding

Label claim, mg/capsule

20.256 ± 0.066

(101.282%)

20.222 ± 0.163

(101.108%)

19.961 ± 0.668

(99.807%)

17.780 ± 1.605

(88.902%)

Study Author Conclusions

Results from this study found that the enteric coating of duloxetine pellets mixed with applesauce or apple juice was not negatively affected. ​Mixing duloxetine pellets with applesauce or apple juice appears to be an acceptable vehicle for administration. However, exposing the pellets to chocolate pudding damaged the pellets' enteric coating.

InpharmD Researcher Critique

Although the duloxetine pallets were not affected after 2 hours exposure to apple juice, the study did not investigate administering duloxetine via a nasogatric tube.