A 37-year-old female with a history of lupus is admitted to the hospital with rash, arthralgias, and altered mental status. On examination, the patient displays stupor, mutism, posturing, and echopraxia while vital signs, creatine kinase, and brain MRI are all normal. Lorazepam 2mg IV q6 partially improves her symptoms, but higher doses cause more sedation. How would you proceed?
Answer A. Augmentation with memantine
A variety of medical conditions can produce stupor, which is a decreased awareness and interaction with the external environment. Stupor can occur with preserved alertness, more often seen in catatonia, or with lethargy, more often seen in delirium. Differences between etiologies (psychiatric vs medical) do not appear to alter the general treatment approach for catatonia. Removal of suspected offending agents, treatment of the underlying medical condition, or management of drug withdrawal are essential.
Potential adverse effects of high-dose intravenous lorazepam include anion gap acidosis from its solvent, propylene glycol. This risk increases with higher doses and in renal impairment, but toxicity has been reported with as little as 2 mg per hour. The osmolar gap (a marker for glycol toxicity) should be monitored every other day if the lorazepam infusion reaches 1 mg/kg daily.
Augmentation with memantine or amantadine may be helpful. Their hypothesized mechanism is N-methyl-d-aspartic acid (NMDA) receptor antagonism, which may be linked to GABA hypofunction. Memantine can be started at 5 to 10 mg daily and titrated based on medical status with monitoring of the QT interval. Improvement from memantine seems slower than with lorazepam, but both can be co-administered. Amantadine is started at 100 to 200 mg daily and titrated, but it should be used with caution if renal impairment or seizure risk is present. Mania, suicidal ideation, and withdrawal-emergent NMS have also been reported with administration of amantadine.
For more on this topic, see Update on Medical Catatonia: Highlight on Delirium, by Jo Ellen Wilson, MD, MPH, Lex Denysenko, MD, and Andrew Francis, PhD, MD, on which this quiz is based.