Pretest self-assessment question (answer at the end of the case)
Clozapine (Clozaril)-induced sialorrhea (CIS), or excessive drooling, is caused by what theoretical pharmacologic mechanism?
A. Dopamine-2 receptor antagonism
B. Alpha-2 receptor antagonism
C. Serotonin-2A receptor antagonism
D. Muscarinic-3 receptor antagonism
E. B and D
F. A and C
G. All of the above
Patient evaluation on intake
26-year-old man met initially on an inpatient unit while paranoid
Psychiatric history
This patient was admitted to a psychiatric inpatient unit in the middle of a second paranoid psychotic schizophrenia episode
Symptoms consisted mainly of paranoid- and guilt-based delusions, thought blocking, and mild negative symptoms
During his first psychotic break, he was released after successful inpatient treatment with haloperidol (Haldol) 10 mg/d
Despite this treatment, the symptoms increased to the point of requiring a second inpatient stay where an increase in haloperidol (20 mg/d) was ineffective
At this time, risperidone (Risperdal) was the only atypical antipsychotic available and he was switched and titrated to 6 mg/d with relief of psychosis, and discharged from the hospital
Over the next year while followed in an outpatient setting, he was noted to be very compliant with his medication and appointments
Family was supportive and involved in his care, and he wished to return to college to obtain an advanced degree
Things were going well clinically and psychosocially; discussions were begun about long-term treatment, the risk of TD, and what his wishes were if he began a third psychotic break
Unfortunately, the psychosis returned, and while an inpatient again
– Risperidone (Risperdal) 10–12 mg/d was ineffective, and based upon previous discussions regarding the most effective and least TD-prone antipsychotic and with written advanced treatment, Psychiatric Advance Directives signed by the patient, he was started on clozapine (Clozaril), which was titrated to 400 mg/d
– Psychosis resolved
– Has been relatively symptom free for several years
– Plasma levels are therapeutic at 500 ng/ml (levels >350 ng/ml have been shown to be clinically effective)
– White blood cells have been stable (>3000/mL)
– Mild sedation and moderate CIS are experienced
Question
Of the following choices, what would you do?
Lower the clozapine (Clozaril) to lower CIS while trying to maintain a reasonable blood level to avoid breakthrough psychosis
Lower the clozapine (Clozaril) to lower CIS while trying to maintain a reasonable blood level but combine with another atypical antipsychotic to maintain remission
Lower the clozapine (Clozaril) to lower CIS while trying to maintain a reasonable blood level but combine with a typical antipsychotic to maintain remission
Switch to oral, dissolving clozapine (FazaClo) tablets or liquid clozapine (Versacloz) to lower CIS
Switch to an atypical antipsychotic monotherapy now that more are available
Try to use an augmentation as an antidote to CIS while maintaining his effective current clozapine dose