Clozapine-Induced Cataplexy

SIR: Cataplexy is an abnormal state characterized by atonia and believed to represent dissociated REM (rapid eye movement) phenomena that intrude into wakefulness. Cataplexy-like phenomenon as a rare side effect of clozapine treatment was initially reported by Chiles et al. 1 in a series of four people with schizophrenia who were on variable doses of clozapine. Blum 2 also noted cataplexy during clozapine treatment along with hyperthermia and increased REM sleep. We report another patient presenting with this rare side effect of clozapine and attempt to explain the phenomenon with possible neurobiological mechanisms.

A 29-year-old unmarried woman with unremarkable past, family and personal history presented with an episodic illness of 4 years duration suggestive of schizoaffective disorder, manic type. As she remained symptomatic even after adequate trials with various antipsychotics along with mood stabilizers, clozapine was introduced. She was on a regimen of sodium valproate, 1000mg/day, when clozapine was initiated and gradually hiked to 150mg/day. Though her symptoms decreased significantly, she started complaining of a sudden onset of knee-buckling along with dropping objects, which was not associated with any emotional trigger, loss of awareness, or falling. She did not complain of sleep troubles at that time. The phenomenon started occurring in the first week after reaching 150mg/day and was taking place two to three times per day. A detailed neurological examination and laboratory work-up were unremarkable. Valproate serum levels were at 120 and 125μg/dl on two different occasions. A 32-channel 1-hour EEG (electroencephalogram) study revealed background slowing in 4.5–5 Hz theta range with no epileptiform abnormality. Clozapine was reduced to 125mg/day and cataplectic attacks decreased in frequency to one to two attacks on alternate days. Repeat EEG after a month was similar to the previous one. Increasing the dose of sodium valproate to 1200mg/day did not alter the frequency of such attacks. Because she continued to drop objects, administration of clozapine was stopped, followed by complete cessation of cataplexy attacks.