Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

Table 1

Published cases of catatonia associated with clozapine withdrawal identified by PubMed search.

Authors	Country	Age	Sex	Dx	Clozapine		DSM-5 criteria for catatonia^3	Modified Liverpool ADR Causality Category^4
					Dose (mg/day)	Onset^2 (days)
Lee and Robertson [15]	New Zealand	30	M	S	350	1.5	Yes	Probable
Yeh et al. [16]	Taiwan	55	M	S	400	7	Yes	Definite
Bastiampillai et al. [17]	Australia	58	F	SA	300	3	Yes	Definite
Thanasan and Jambunathan [18]	Malaysia	ND^5	M	SA	200	7	Yes	Probable
Wadekar and Syed [19]	USA	49	F	S	550	5	Yes^6	Probable
Kumar et al. [20]	India	29	M	S	250	2	Yes	Probable
Wang et al. [21]	Australia	39	F	S	200	Immediate^7	Yes	Definite
Shahrour et al. [22]	UAE	32	M	S	400	>28^8	No^8	Unlikely
Koychev et al. [23]	UK	22	M	PI	300	4	Unknown^9	Unknown^9

ADR: adverse drug reaction; DSM-5: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; Dx: underlying psychiatric diagnosis; F: female; M: male; ND: not described; PI: psychotic illness; S: schizophrenia; SA: schizoaffective; UAE: United Arab Emirates; UK: United Kingdom; USA: United States of America.
On 9/8/16, a PubMed search with the words “catatonia AND clozapine” was completed. We obtained 58 abstracts. All of them were reviewed for cases of catatonia after clozapine withdrawal. If the abstract or title appeared relevant, we obtained the article. After reviewing all articles, we identified these 9 cases of possible catatonia after clozapine withdrawal.
Onset refers to the time period (measured in days) between sudden clozapine withdrawal and catatonia symptoms.
The first and last authors determined whether a patient met Criterion A for DSM-5 catatonia (≥3 of 12 symptoms).
The first and last authors developed the Modified Liverpool ADR Causality Assessment Tool to accommodate an ADR secondary to drug withdrawal. After reviewing each case and discussing it, the first and last authors selected a causality category by agreement. The flow chart of each case is available in the Supplementary Material.
The patient is described as middle-aged.
Catatonic symptoms were not described. The authors used the Bush-Francis scale in which 6/14 items on the screening instrument (a truncated version of the 23-item scale) were positive (≥2 is considered positive).
The article described the patient as having been episodically noncompliant with clozapine. On four previous occasions in the immediate period following clozapine cessation, the patient developed florid psychotic symptoms in the form of persecutory, grandiose delusions, disorganized behavior, and auditory hallucinations. She displayed catatonic features (Bush-Francis scale score of 20, indicating severe catatonia) with excitement, mutism, posturing, staring, negativism, and echolalia.
The patient was originally on clozapine and olanzapine. Both were stopped 4 weeks before symptoms. Then, he was restarted only on olanzapine and was discharged; 4 weeks later, he presented to the emergency room with symptoms. All the unusual symptoms described by the authors occurred after olanzapine withdrawal. The authors did not provide enough information for us to diagnose catatonia according to DSM-5 criteria; 1 of 12 DSM-5 catatonia symptoms was provided.
We could not make a definitive judgment in this case. The article focused on an episode of clozapine withdrawal which was considered as potential neuroleptic malignant syndrome but the authors did not provide enough information for us to diagnose catatonia according to DSM-5 criteria. Another prior withdrawal episode after several days of clozapine cessation only described the patient’s stupor, rigidity, and mutism, providing 2 of 12 DSM-5 catatonia symptoms.