(012) Parkinsonism is a Red Herring: Broad Differential Diagnoses in a Case of Catatonia Secondary to Clozapine Withdrawal

Location: Griffin Hall

Trainee Involvement: Yes

Presenting Author(s)

Chin Kuo, MD

Psychiatry Resident
Maimonides Medical Center
Brooklyn, New York, United States

Co-Author(s)

Sara V. Carlini, MD

Psychiatrist, Consultation-Liaison Psychiatry Department
Maimonides Medical Center
Brooklyn, New York, United States
Shruti Tiwari, M.D.

Director of Consultation-Liaison Psychiatry
Maimonides Medical Center
Long Island City, New York, United States

Background: Catatonia is a neuropsychiatric syndrome rarely caused by clozapine withdrawal. Although the underlying mechanisms of clozapine withdrawal catatonia are not clear, the effects of clozapine on GABA interneurons may be implicated. (1) Clozapine withdrawal catatonia often responds poorly to lorazepam but studies show effective response by reintroducing clozapine. (1-2)

Case: A 56-year-old woman with a history of schizophrenia treated with an outpatient regimen of intramuscular (IM) haloperidol decanoate 150mg monthly (last administered 2 weeks before admission), valproic acid (VPA) 1250mg orally daily, and clozapine 200mg orally at bedtime, presented to the emergency department (ED) with resting tremors in the extremities. Collateral reported patient had discontinued clozapine, believing it was causing tremors
In the ED, the patient was noted to be staring, hypoactive, and rigid, with a Bush Francis Catatonia Rating Scale (BFCRS) score of 13. There was no significant improvement after two doses of IM lorazepam 2mg. Patient was started on intravenous (IV) lorazepam 2mg twice per day (BID) for catatonia and IV benztropine 1mg BID for Parkinsonism.
Upon admission to Medicine, catatonia symptoms worsened to a BFCRS score of 17. She exhibited worsening immobility and withdrawal, necessitating nasogastric (NG) tube placement. Additionally, the patient developed a febrile episode to 101.3°F, intermittent tachycardia, and decreased urine output. Lab tests revealed elevated ammonia (72), VPA (109.9), and creatine phosphokinase levels (643). Urinalysis showed positive leukocyte esterase. Other work-up, including head CT, brain MRI, lumbar puncture, and EEG, were noncontributory.
Benztropine was discontinued due to concern of anticholinergic side effects, VPA was held for hyperammonemia. Ceftriaxone was started to treat urinary tract infection. Lorazepam was gradually titrated to 3mg IV four times per day over the first week of admission, but the patient’s catatonia symptoms did not improve, and she appeared oversedated.
Given lack of response to lorazepam, clozapine was restarted at 25mg at bedtime once NG tube was placed and increased by 25mg every two days. Four days after clozapine was reintroduced, she began to show improvements in voluntary movements. A week later, her catatonia completely resolved and her vitals stabilized.
Discussion: This case presents a complex clinical scenario in which no single diagnosis fully accounted for the presenting symptoms. Differential diagnoses included delirium, idiopathic Parkinsonism, medication-induced Parkinsonism, neuroleptic malignant syndrome, stroke, and seizures. The case underscores the importance of recognizing clozapine withdrawal catatonia and managing it appropriately with clozapine reintroduction, as case report data has suggested that benzodiazepines alone may not be sufficient for management (1).

Conclusion: Early reinitiation of clozapine should be considered when clozapine withdrawal is a suspected etiology of catatonia.

References:

1) Lander M, Bastiampillai T, Sareen J. Review of withdrawal catatonia: what does this reveal about clozapine? Transl Psychiatry. 2018 Jul 31;8(1):139. doi: 10.1038/s41398-018-0192-9. PMID: 30065280; PMCID: PMC6068101.

2) Boazak M, Cotes RO, Potvin H, Decker AM, Schwartz AC. Catatonia Due to Clozapine Withdrawal: A Case Report and Literature Review. Psychosomatics. 2019 Jul-Aug;60(4):421-427. doi: 10.1016/j.psym.2018.07.010. Epub 2018 Jul 29. PMID: 30268340.